chr4-2831661-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001122681.2(SH3BP2):c.1332G>C(p.Ser444Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S444S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SH3BP2
NM_001122681.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12

Publications

2 publications found

Variant links:

Genes affected

SH3BP2 (HGNC:10825): (SH3 domain binding protein 2) The protein encoded by this gene has an N-terminal pleckstrin homology (PH) domain, an SH3-binding proline-rich region, and a C-terminal SH2 domain. The protein binds to the SH3 domains of several proteins including the ABL1 and SYK protein tyrosine kinases , and functions as a cytoplasmic adaptor protein to positively regulate transcriptional activity in T, natural killer (NK), and basophilic cells. Mutations in this gene result in cherubism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

SH3BP2 Gene-Disease associations (from GenCC):

cherubism
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

SH3BP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-2831661-G-C is Benign according to our data. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-2831661-G-C is described in CliVar as Likely_benign. Clinvar id is 2084949.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2 link	c.1332G>C	p.Ser444Ser	synonymous_variant	Exon 9 of 13	ENST00000503393.8	NP_001116153.1	P78314-1A0A384N6E5
SH3BP2	NM_001145856.2 link	c.1503G>C	p.Ser501Ser	synonymous_variant	Exon 9 of 13		NP_001139328.1	P78314-4
SH3BP2	NM_001145855.2 link	c.1416G>C	p.Ser472Ser	synonymous_variant	Exon 9 of 13		NP_001139327.1	P78314-3
SH3BP2	NM_003023.4 link	c.1332G>C	p.Ser444Ser	synonymous_variant	Exon 9 of 13		NP_003014.3	P78314-1A0A384N6E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8 link	c.1332G>C	p.Ser444Ser	synonymous_variant	Exon 9 of 13	1	NM_001122681.2	ENSP00000422168.3		P78314-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000481

AC:

AN:

207880

AF XY:

0.00000889

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1437356

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32828

American (AMR)

AF:

0.00

AC:

AN:

41998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25740

East Asian (EAS)

AF:

0.00

AC:

AN:

38238

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1099246

Other (OTH)

AF:

0.00

AC:

AN:

59386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Fibrous dysplasia of jaw

Benign:1

Jan 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0030

(source)

DANN

Benign

0.42

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over