4-2827682-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001122681.2(SH3BP2):c.586+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 1,569,274 control chromosomes in the GnomAD database, including 7,286 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1940 hom., cov: 34)

Exomes 𝑓: 0.076 ( 5346 hom. )

Consequence

SH3BP2
NM_001122681.2 splice_region, intron

Scores

Splicing: ADA: 0.001347

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.26

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

cherubism
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

SH3BP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 4-2827682-G-A is Benign according to our data. Variant chr4-2827682-G-A is described in ClinVar as [Benign]. Clinvar id is 258897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2 link	c.586+8G>A	splice_region_variant, intron_variant	Intron 7 of 12	ENST00000503393.8	NP_001116153.1	P78314-1A0A384N6E5
SH3BP2	NM_001145856.2 link	c.757+8G>A	splice_region_variant, intron_variant	Intron 7 of 12		NP_001139328.1	P78314-4
SH3BP2	NM_001145855.2 link	c.670+8G>A	splice_region_variant, intron_variant	Intron 7 of 12		NP_001139327.1	P78314-3
SH3BP2	NM_003023.4 link	c.586+8G>A	splice_region_variant, intron_variant	Intron 7 of 12		NP_003014.3	P78314-1A0A384N6E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8 link	c.586+8G>A		splice_region_variant, intron_variant	Intron 7 of 12	1	NM_001122681.2	ENSP00000422168.3		P78314-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19268

AN:

152106

Hom.:

1933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.0572

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.110

GnomAD2 exomes

AF:

0.0964

AC:

17727

AN:

183976

AF XY:

0.0929

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.0645

Gnomad EAS exome

AF:

0.0651

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0694

Gnomad OTH exome

AF:

0.0924

GnomAD4 exome

AF:

0.0763

AC:

108100

AN:

1417050

Hom.:

5346

Cov.:

AF XY:

0.0763

AC XY:

53551

AN XY:

701474

show subpopulations

African (AFR)

AF:

0.287

AC:

9385

AN:

32662

American (AMR)

AF:

0.140

AC:

5473

AN:

38964

Ashkenazi Jewish (ASJ)

AF:

0.0635

AC:

1610

AN:

25354

East Asian (EAS)

AF:

0.0584

AC:

2206

AN:

37802

South Asian (SAS)

AF:

0.114

AC:

9244

AN:

81062

European-Finnish (FIN)

AF:

0.0198

AC:

1002

AN:

50630

Middle Eastern (MID)

AF:

0.107

AC:

611

AN:

5706

European-Non Finnish (NFE)

AF:

0.0677

AC:

73510

AN:

1086208

Other (OTH)

AF:

0.0862

AC:

5059

AN:

58662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.578

Heterozygous variant carriers

4021

8043

12064

16086

20107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.127

AC:

19303

AN:

152224

Hom.:

1940

Cov.:

AF XY:

0.124

AC XY:

9226

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.274

AC:

11390

AN:

41496

American (AMR)

AF:

0.124

AC:

1891

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0741

AC:

257

AN:

3468

East Asian (EAS)

AF:

0.0574

AC:

297

AN:

5178

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4826

European-Finnish (FIN)

AF:

0.0182

AC:

193

AN:

10620

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0651

AC:

4425

AN:

68012

Other (OTH)

AF:

0.109

AC:

230

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

806

1611

2417

3222

4028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0696

Hom.:

317

Bravo

AF:

0.141

Asia WGS

AF:

0.107

AC:

375

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fibrous dysplasia of jaw

Benign:2

Jan 12, 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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.79

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

4-2827682-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over