chr4-2820740-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001122681.2(SH3BP2):c.123G>T(p.Leu41Leu) 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

Publications

22 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 -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 VariationId is 258893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2 link	c.123G>T	p.Leu41Leu	synonymous_variant	Exon 2 of 13	ENST00000503393.8	NP_001116153.1	P78314-1A0A384N6E5
SH3BP2	NM_001145856.2 link	c.294G>T	p.Leu98Leu	synonymous_variant	Exon 2 of 13		NP_001139328.1	P78314-4
SH3BP2	NM_001145855.2 link	c.207G>T	p.Leu69Leu	synonymous_variant	Exon 2 of 13		NP_001139327.1	P78314-3
SH3BP2	NM_003023.4 link	c.123G>T	p.Leu41Leu	synonymous_variant	Exon 2 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.123G>T	p.Leu41Leu	synonymous_variant	Exon 2 of 13	1	NM_001122681.2	ENSP00000422168.3		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

GnomAD2 exomes

AF:

0.453

AC:

112803

AN:

249080

AF XY:

0.455

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 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

African (AFR)

AF:

0.142

AC:

4766

AN:

33476

American (AMR)

AF:

0.597

AC:

26579

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

10667

AN:

26118

East Asian (EAS)

AF:

0.456

AC:

18075

AN:

39674

South Asian (SAS)

AF:

0.493

AC:

42511

AN:

86234

European-Finnish (FIN)

AF:

0.441

AC:

23521

AN:

53330

Middle Eastern (MID)

AF:

0.394

AC:

2265

AN:

5756

European-Non Finnish (NFE)

AF:

0.449

AC:

498705

AN:

1111340

Other (OTH)

AF:

0.435

AC:

26253

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19248

38495

57743

76990

96238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14980

29960

44940

59920

74900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.374

AC:

56881

AN:

152182

Hom.:

12158

Cov.:

AF XY:

0.380

AC XY:

28243

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.153

AC:

6351

AN:

41536

American (AMR)

AF:

0.517

AC:

7908

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

1401

AN:

3468

East Asian (EAS)

AF:

0.463

AC:

2394

AN:

5170

South Asian (SAS)

AF:

0.496

AC:

2391

AN:

4822

European-Finnish (FIN)

AF:

0.438

AC:

4642

AN:

10604

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30288

AN:

67980

Other (OTH)

AF:

0.383

AC:

807

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1737

3475

5212

6950

8687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.413

Hom.:

13036

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

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fibrous dysplasia of jaw

Benign:3

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

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

May 04, 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

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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

(source)

DANN

Benign

0.79

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

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