Variant 4-2820562-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001122681.2(SH3BP2):c.-4-52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,611,824 control chromosomes in the GnomAD database, including 243,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 22984 hom., cov: 34)

Exomes 𝑓: 0.55 ( 220406 hom. )

Consequence

SH3BP2
NM_001122681.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.32

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-2820562-C-A is Benign according to our data. Variant chr4-2820562-C-A is described in ClinVar as [Benign]. Clinvar id is 1256910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2 link	c.-4-52C>A	intron_variant	Intron 1 of 12	ENST00000503393.8	NP_001116153.1	P78314-1A0A384N6E5
SH3BP2	NM_001145856.2 link	c.168-52C>A	intron_variant	Intron 1 of 12		NP_001139328.1	P78314-4
SH3BP2	NM_001145855.2 link	c.81-52C>A	intron_variant	Intron 1 of 12		NP_001139327.1	P78314-3
SH3BP2	NM_003023.4 link	c.-4-52C>A	intron_variant	Intron 1 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.-4-52C>A		intron_variant	Intron 1 of 12	1	NM_001122681.2	ENSP00000422168.3		P78314-1

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83259

AN:

152048

Hom.:

22959

Cov.:

show subpopulations

Gnomad AFR

AF:

0.542

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.544

GnomAD4 exome

AF:

0.548

AC:

799673

AN:

1459656

Hom.:

220406

AF XY:

0.549

AC XY:

398552

AN XY:

726166

show subpopulations

Gnomad4 AFR exome

AF:

0.534

Gnomad4 AMR exome

AF:

0.672

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.465

Gnomad4 SAS exome

AF:

0.597

Gnomad4 FIN exome

AF:

0.486

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.550

GnomAD4 genome

AF:

0.548

AC:

83325

AN:

152168

Hom.:

22984

Cov.:

AF XY:

0.547

AC XY:

40694

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.542

Gnomad4 AMR

AF:

0.639

Gnomad4 ASJ

AF:

0.549

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.546

Alfa

AF:

0.535

Hom.:

2727

Bravo

AF:

0.559

Asia WGS

AF:

0.551

AC:

1914

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

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 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

DANN

Benign

0.75

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

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