Genetic Variant NM_001122681.2:c.-4-8838C>G (chr4-2811776-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001122681.2(SH3BP2):c.-4-8838C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 157,370 control chromosomes in the GnomAD database, including 33,110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 32001 hom., cov: 33)

Exomes 𝑓: 0.62 ( 1109 hom. )

Consequence

SH3BP2
NM_001122681.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0500

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2 link	c.-4-8838C>G		intron_variant	Intron 1 of 12	ENST00000503393.8	NP_001116153.1	P78314-1A0A384N6E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8 link	c.-4-8838C>G		intron_variant	Intron 1 of 12	1	NM_001122681.2	ENSP00000422168.3		P78314-1

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98305

AN:

151954

Hom.:

31964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.624

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.622

GnomAD4 exome

AF:

0.624

AC:

3307

AN:

5298

Hom.:

1109

Cov.:

AF XY:

0.627

AC XY:

1751

AN XY:

2792

show subpopulations

African (AFR)

AF:

0.591

AC:

AN:

American (AMR)

AF:

0.751

AC:

1038

AN:

1382

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

AN:

East Asian (EAS)

AF:

0.458

AC:

AN:

216

South Asian (SAS)

AF:

0.677

AC:

405

AN:

598

European-Finnish (FIN)

AF:

0.607

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.562

AC:

1551

AN:

2760

Other (OTH)

AF:

0.657

AC:

151

AN:

230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.647

AC:

98391

AN:

152072

Hom.:

32001

Cov.:

AF XY:

0.650

AC XY:

48331

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.693

AC:

28759

AN:

41476

American (AMR)

AF:

0.723

AC:

11052

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2204

AN:

3472

East Asian (EAS)

AF:

0.539

AC:

2790

AN:

5172

South Asian (SAS)

AF:

0.698

AC:

3368

AN:

4826

European-Finnish (FIN)

AF:

0.624

AC:

6597

AN:

10564

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.611

AC:

41503

AN:

67964

Other (OTH)

AF:

0.626

AC:

1322

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1799

3597

5396

7194

8993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.638

Hom.:

3870

Bravo

AF:

0.654

Asia WGS

AF:

0.661

AC:

2301

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.050

PromoterAI

0.047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over