rs16843413

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001122681.2(SH3BP2):c.417C>G(p.Pro139Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,580,238 control chromosomes in the GnomAD database, including 6,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1815 hom., cov: 34)

Exomes 𝑓: 0.075 ( 5118 hom. )

Consequence

SH3BP2
NM_001122681.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.51

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-2825185-C-G is Benign according to our data. Variant chr4-2825185-C-G is described in ClinVar as [Benign]. Clinvar id is 258896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2 link	c.417C>G	p.Pro139Pro	synonymous_variant	Exon 5 of 13	ENST00000503393.8	NP_001116153.1	P78314-1A0A384N6E5
SH3BP2	NM_001145856.2 link	c.588C>G	p.Pro196Pro	synonymous_variant	Exon 5 of 13		NP_001139328.1	P78314-4
SH3BP2	NM_001145855.2 link	c.501C>G	p.Pro167Pro	synonymous_variant	Exon 5 of 13		NP_001139327.1	P78314-3
SH3BP2	NM_003023.4 link	c.417C>G	p.Pro139Pro	synonymous_variant	Exon 5 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.417C>G	p.Pro139Pro	synonymous_variant	Exon 5 of 13	1	NM_001122681.2	ENSP00000422168.3		P78314-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18703

AN:

152056

Hom.:

1808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.0557

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0650

Gnomad OTH

AF:

0.108

GnomAD2 exomes

AF:

0.0885

AC:

17180

AN:

194026

AF XY:

0.0857

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.0629

Gnomad EAS exome

AF:

0.0599

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.0628

Gnomad OTH exome

AF:

0.0864

GnomAD4 exome

AF:

0.0753

AC:

107489

AN:

1428062

Hom.:

5118

Cov.:

AF XY:

0.0753

AC XY:

53297

AN XY:

707406

show subpopulations

African (AFR)

AF:

0.273

AC:

8877

AN:

32534

American (AMR)

AF:

0.136

AC:

5434

AN:

39874

Ashkenazi Jewish (ASJ)

AF:

0.0633

AC:

1617

AN:

25540

East Asian (EAS)

AF:

0.0550

AC:

2076

AN:

37726

South Asian (SAS)

AF:

0.113

AC:

9223

AN:

81762

European-Finnish (FIN)

AF:

0.0196

AC:

996

AN:

50926

Middle Eastern (MID)

AF:

0.105

AC:

602

AN:

5718

European-Non Finnish (NFE)

AF:

0.0673

AC:

73701

AN:

1094960

Other (OTH)

AF:

0.0841

AC:

4963

AN:

59022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

5193

10386

15580

20773

25966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.123

AC:

18738

AN:

152176

Hom.:

1815

Cov.:

AF XY:

0.120

AC XY:

8964

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.262

AC:

10888

AN:

41492

American (AMR)

AF:

0.121

AC:

1848

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0741

AC:

257

AN:

3470

East Asian (EAS)

AF:

0.0558

AC:

288

AN:

5160

South Asian (SAS)

AF:

0.113

AC:

545

AN:

4826

European-Finnish (FIN)

AF:

0.0183

AC:

194

AN:

10622

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0650

AC:

4417

AN:

67988

Other (OTH)

AF:

0.107

AC:

225

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

802

1604

2405

3207

4009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0799

Hom.:

236

Bravo

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fibrous dysplasia of jaw

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.2

(source)

DANN

Benign

0.59

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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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rs16843413

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over