rs16843413

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).

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. Variant chr4-2825185-C-G is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.0885

AC:

17180

AN:

194026

Hom.:

1082

AF XY:

0.0857

AC XY:

8938

AN XY:

104354

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 SAS exome

AF:

0.112

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

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.0633

Gnomad4 EAS exome

AF:

0.0550

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.0196

Gnomad4 NFE exome

AF:

0.0673

Gnomad4 OTH exome

AF:

0.0841

GnomAD4 genome

AF:

0.123

AC:

18738

AN:

152176

Hom.:

1815

Cov.:

AF XY:

0.120

AC XY:

8964

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.0741

Gnomad4 EAS

AF:

0.0558

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.0650

Gnomad4 OTH

AF:

0.107

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

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.2

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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