rs231402

Positions:

chr4-2820740-G-T

Variant summary

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

The NM_001122681.2(SH3BP2):c.123G>T(p.Leu41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,612,980 control chromosomes in the GnomAD database, including 161,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 12158 hom., cov: 34)

Exomes 𝑓: 0.45 ( 149136 hom. )

Consequence

SH3BP2
NM_001122681.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 2.21

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=-0.55).

BP6

Variant 4-2820740-G-T is Benign according to our data. Variant chr4-2820740-G-T is described in ClinVar as [Benign]. Clinvar id is 258893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-2820740-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SH3BP2	NM_001122681.2 linkuse as main transcript	c.123G>T	p.Leu41=	synonymous_variant	2/13	ENST00000503393.8
SH3BP2	NM_001145856.2 linkuse as main transcript	c.294G>T	p.Leu98=	synonymous_variant	2/13
SH3BP2	NM_001145855.2 linkuse as main transcript	c.207G>T	p.Leu69=	synonymous_variant	2/13
SH3BP2	NM_003023.4 linkuse as main transcript	c.123G>T	p.Leu41=	synonymous_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8 linkuse as main transcript	c.123G>T	p.Leu41=	synonymous_variant	2/13	1	NM_001122681.2	P2	P78314-1

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56862

AN:

152064

Hom.:

12148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.381

GnomAD3 exomes

AF:

0.453

AC:

112803

AN:

249080

Hom.:

26909

AF XY:

0.455

AC XY:

61294

AN XY:

134702

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.605

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.448

Gnomad OTH exome

AF:

0.455

GnomAD4 exome

AF:

0.447

AC:

653342

AN:

1460798

Hom.:

149136

Cov.:

AF XY:

0.449

AC XY:

325965

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.408

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.441

Gnomad4 NFE exome

AF:

0.449

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.374

AC:

56881

AN:

152182

Hom.:

12158

Cov.:

AF XY:

0.380

AC XY:

28243

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.517

Gnomad4 ASJ

AF:

0.404

Gnomad4 EAS

AF:

0.463

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.438

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.420

Hom.:

8953

Bravo

AF:

0.372

Asia WGS

AF:

0.477

AC:

1658

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 84% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -
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 -

Fibrous dysplasia of jaw

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.55

CADD

Benign

9.6

DANN

Benign

0.79

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