Variant 4-2818442-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000503393.8(SH3BP2):c.-4-2172C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,006,900 control chromosomes in the GnomAD database, including 5,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 855 hom., cov: 33)

Exomes 𝑓: 0.098 ( 4260 hom. )

Consequence

SH3BP2
ENST00000503393.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.83

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-2818442-C-G is Benign according to our data. Variant chr4-2818442-C-G is described in ClinVar as [Benign]. Clinvar id is 1226123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SH3BP2	NM_001122681.2 linkuse as main transcript	c.-4-2172C>G	intron_variant	ENST00000503393.8	NP_001116153.1
SH3BP2	NM_001145855.2 linkuse as main transcript	c.81-2172C>G	intron_variant		NP_001139327.1
SH3BP2	NM_001145856.2 linkuse as main transcript	c.167+52C>G	intron_variant		NP_001139328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8 linkuse as main transcript	c.-4-2172C>G		intron_variant		1	NM_001122681.2	ENSP00000422168	P2	P78314-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15351

AN:

151474

Hom.:

855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0913

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.0832

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.0921

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.0984

AC:

84147

AN:

855320

Hom.:

4260

AF XY:

0.0990

AC XY:

40076

AN XY:

404970

show subpopulations

Gnomad4 AFR exome

AF:

0.0955

Gnomad4 AMR exome

AF:

0.0567

Gnomad4 ASJ exome

AF:

0.0924

Gnomad4 EAS exome

AF:

0.00444

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.0904

GnomAD4 genome

AF:

0.101

AC:

15352

AN:

151580

Hom.:

855

Cov.:

AF XY:

0.103

AC XY:

7662

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.0912

Gnomad4 AMR

AF:

0.0705

Gnomad4 ASJ

AF:

0.0832

Gnomad4 EAS

AF:

0.0109

Gnomad4 SAS

AF:

0.0922

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0519

Hom.:

Bravo

AF:

0.0915

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

DANN

Benign

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over