chr4-2824649-C-T

Position:

chr4-2824649-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001122681.2(SH3BP2):c.276C>T(p.Asn92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,613,440 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 33 hom., cov: 33)

Exomes 𝑓: 0.022 ( 430 hom. )

Consequence

SH3BP2
NM_001122681.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.11

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 -16 ACMG points.

BP6

Variant 4-2824649-C-T is Benign according to our data. Variant chr4-2824649-C-T is described in ClinVar as [Benign]. Clinvar id is 348569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-2824649-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0155 (2367/152294) while in subpopulation NFE AF= 0.0247 (1679/68008). AF 95% confidence interval is 0.0237. There are 33 homozygotes in gnomad4. There are 1079 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2367 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SH3BP2	NM_001122681.2 linkuse as main transcript	c.276C>T	p.Asn92=	synonymous_variant	4/13	ENST00000503393.8
SH3BP2	NM_001145856.2 linkuse as main transcript	c.447C>T	p.Asn149=	synonymous_variant	4/13
SH3BP2	NM_001145855.2 linkuse as main transcript	c.360C>T	p.Asn120=	synonymous_variant	4/13
SH3BP2	NM_003023.4 linkuse as main transcript	c.276C>T	p.Asn92=	synonymous_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8 linkuse as main transcript	c.276C>T	p.Asn92=	synonymous_variant	4/13	1	NM_001122681.2	P2	P78314-1

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2367

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0143

AC:

3596

AN:

251134

Hom.:

AF XY:

0.0142

AC XY:

1934

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.00960

Gnomad ASJ exome

AF:

0.00715

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0235

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0219

AC:

31938

AN:

1461146

Hom.:

430

Cov.:

AF XY:

0.0211

AC XY:

15346

AN XY:

726926

show subpopulations

Gnomad4 AFR exome

AF:

0.00355

Gnomad4 AMR exome

AF:

0.00977

Gnomad4 ASJ exome

AF:

0.00700

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00262

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0262

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0155

AC:

2367

AN:

152294

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1079

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00602

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0247

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0266

EpiControl

AF:

0.0250

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fibrous dysplasia of jaw

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: 16

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