Variant chr4-2818534-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001122681.2(SH3BP2):c.-4-2080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 521,254 control chromosomes in the GnomAD database, including 2,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 865 hom., cov: 33)

Exomes 𝑓: 0.085 ( 1579 hom. )

Consequence

SH3BP2
NM_001122681.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.510

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 4-2818534-G-A is Benign according to our data. Variant chr4-2818534-G-A is described in ClinVar as [Benign]. Clinvar id is 1264442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SH3BP2	NM_001122681.2 linkuse as main transcript	c.-4-2080G>A	intron_variant	ENST00000503393.8
SH3BP2	NM_001145855.2 linkuse as main transcript	c.81-2080G>A	intron_variant
SH3BP2	NM_001145856.2 linkuse as main transcript	c.167+144G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8 linkuse as main transcript	c.-4-2080G>A		intron_variant		1	NM_001122681.2	P2	P78314-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15466

AN:

152114

Hom.:

865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0917

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0710

Gnomad ASJ

AF:

0.0861

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.0904

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.0847

AC:

31248

AN:

369032

Hom.:

1579

AF XY:

0.0851

AC XY:

15160

AN XY:

178056

show subpopulations

Gnomad4 AFR exome

AF:

0.0775

Gnomad4 AMR exome

AF:

0.0517

Gnomad4 ASJ exome

AF:

0.0798

Gnomad4 EAS exome

AF:

0.00436

Gnomad4 SAS exome

AF:

0.0815

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.0860

Gnomad4 OTH exome

AF:

0.0768

GnomAD4 genome

AF:

0.102

AC:

15466

AN:

152222

Hom.:

865

Cov.:

AF XY:

0.104

AC XY:

7719

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0915

Gnomad4 AMR

AF:

0.0710

Gnomad4 ASJ

AF:

0.0861

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.0902

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0660

Hom.:

Bravo

AF:

0.0918

Asia WGS

AF:

0.0540

AC:

189

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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