rs3213501

Positions:

chr4-2824673-T-C

Variant summary

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

The NM_001122681.2(SH3BP2):c.300T>C(p.His100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,613,482 control chromosomes in the GnomAD database, including 442,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49106 hom., cov: 32)

Exomes 𝑓: 0.73 ( 393109 hom. )

Consequence

SH3BP2
NM_001122681.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 2.40

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 4-2824673-T-C is Benign according to our data. Variant chr4-2824673-T-C is described in ClinVar as [Benign]. Clinvar id is 258894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-2824673-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SH3BP2	NM_001122681.2 linkuse as main transcript	c.300T>C	p.His100=	synonymous_variant	4/13	ENST00000503393.8
SH3BP2	NM_001145856.2 linkuse as main transcript	c.471T>C	p.His157=	synonymous_variant	4/13
SH3BP2	NM_001145855.2 linkuse as main transcript	c.384T>C	p.His128=	synonymous_variant	4/13
SH3BP2	NM_003023.4 linkuse as main transcript	c.300T>C	p.His100=	synonymous_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8 linkuse as main transcript	c.300T>C	p.His100=	synonymous_variant	4/13	1	NM_001122681.2	P2	P78314-1

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120842

AN:

151986

Hom.:

49039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.951

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.855

Gnomad ASJ

AF:

0.743

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.799

Gnomad FIN

AF:

0.682

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.725

Gnomad OTH

AF:

0.783

GnomAD3 exomes

AF:

0.755

AC:

189528

AN:

251054

Hom.:

72925

AF XY:

0.752

AC XY:

102041

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.956

Gnomad AMR exome

AF:

0.887

Gnomad ASJ exome

AF:

0.729

Gnomad EAS exome

AF:

0.528

Gnomad SAS exome

AF:

0.811

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.724

Gnomad OTH exome

AF:

0.762

GnomAD4 exome

AF:

0.731

AC:

1067538

AN:

1461378

Hom.:

393109

Cov.:

AF XY:

0.732

AC XY:

532408

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.961

Gnomad4 AMR exome

AF:

0.882

Gnomad4 ASJ exome

AF:

0.731

Gnomad4 EAS exome

AF:

0.532

Gnomad4 SAS exome

AF:

0.811

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.719

Gnomad4 OTH exome

AF:

0.744

GnomAD4 genome

AF:

0.795

AC:

120967

AN:

152104

Hom.:

49106

Cov.:

AF XY:

0.794

AC XY:

59003

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.951

Gnomad4 AMR

AF:

0.855

Gnomad4 ASJ

AF:

0.743

Gnomad4 EAS

AF:

0.542

Gnomad4 SAS

AF:

0.798

Gnomad4 FIN

AF:

0.682

Gnomad4 NFE

AF:

0.725

Gnomad4 OTH

AF:

0.785

Alfa

AF:

0.745

Hom.:

71140

Bravo

AF:

0.813

Asia WGS

AF:

0.732

AC:

2546

AN:

3478

EpiCase

AF:

0.741

EpiControl

AF:

0.739

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. -

Fibrous dysplasia of jaw

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 2020	- -
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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.7

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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