4-2829656-T-G

Position:

chr4-2829656-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001122681.2(SH3BP2):c.750T>G(p.Ala250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,611,582 control chromosomes in the GnomAD database, including 200,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A250A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.47 ( 17057 hom., cov: 29)

Exomes 𝑓: 0.50 ( 183226 hom. )

Consequence

SH3BP2
NM_001122681.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.742

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-2829656-T-G is Benign according to our data. Variant chr4-2829656-T-G is described in ClinVar as [Benign]. Clinvar id is 258898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-2829656-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.742 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SH3BP2	NM_001122681.2 linkuse as main transcript	c.750T>G	p.Ala250=	synonymous_variant	8/13	ENST00000503393.8
SH3BP2	NM_001145856.2 linkuse as main transcript	c.921T>G	p.Ala307=	synonymous_variant	8/13
SH3BP2	NM_001145855.2 linkuse as main transcript	c.834T>G	p.Ala278=	synonymous_variant	8/13
SH3BP2	NM_003023.4 linkuse as main transcript	c.750T>G	p.Ala250=	synonymous_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8 linkuse as main transcript	c.750T>G	p.Ala250=	synonymous_variant	8/13	1	NM_001122681.2	P2	P78314-1

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

70975

AN:

151152

Hom.:

17042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.475

GnomAD3 exomes

AF:

0.509

AC:

127187

AN:

250048

Hom.:

33145

AF XY:

0.509

AC XY:

69007

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.642

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.499

AC:

728086

AN:

1460314

Hom.:

183226

Cov.:

AF XY:

0.500

AC XY:

363530

AN XY:

726488

show subpopulations

Gnomad4 AFR exome

AF:

0.371

Gnomad4 AMR exome

AF:

0.635

Gnomad4 ASJ exome

AF:

0.487

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.564

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.495

Gnomad4 OTH exome

AF:

0.498

GnomAD4 genome

AF:

0.470

AC:

71021

AN:

151268

Hom.:

17057

Cov.:

AF XY:

0.473

AC XY:

34933

AN XY:

73864

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.491

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.558

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.494

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.490

Hom.:

30048

Bravo

AF:

0.475

Asia WGS

AF:

0.528

AC:

1835

AN:

3478

EpiCase

AF:

0.496

EpiControl

AF:

0.492

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fibrous dysplasia of jaw

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jul 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.3

DANN

Benign

0.35

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