Variant chr4-2812421-A-G 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.-4-8193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,550,288 control chromosomes in the GnomAD database, including 3,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 1350 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1849 hom. )

Consequence

SH3BP2
NM_001122681.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

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=-0.92).

BP6

Variant 4-2812421-A-G is Benign according to our data. Variant chr4-2812421-A-G is described in ClinVar as [Benign]. Clinvar id is 1239506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-2812421-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BP2	NM_001122681.2 linkuse as main transcript	c.-4-8193A>G		intron_variant		ENST00000503393.8
SH3BP2	NM_001145855.2 linkuse as main transcript	c.24A>G	p.Thr8=	synonymous_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8 linkuse as main transcript	c.-4-8193A>G		intron_variant		1	NM_001122681.2	P2	P78314-1

Frequencies

GnomAD3 genomes

AF:

0.0913

AC:

13888

AN:

152092

Hom.:

1343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0781

Gnomad ASJ

AF:

0.0424

Gnomad EAS

AF:

0.0400

Gnomad SAS

AF:

0.0245

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0695

GnomAD3 exomes

AF:

0.0504

AC:

7552

AN:

149768

Hom.:

415

AF XY:

0.0449

AC XY:

3610

AN XY:

80414

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.0981

Gnomad ASJ exome

AF:

0.0402

Gnomad EAS exome

AF:

0.0396

Gnomad SAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0358

AC:

50002

AN:

1398078

Hom.:

1849

Cov.:

AF XY:

0.0344

AC XY:

23713

AN XY:

689600

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.0945

Gnomad4 ASJ exome

AF:

0.0397

Gnomad4 EAS exome

AF:

0.0618

Gnomad4 SAS exome

AF:

0.0247

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.0281

Gnomad4 OTH exome

AF:

0.0438

GnomAD4 genome

AF:

0.0915

AC:

13925

AN:

152210

Hom.:

1350

Cov.:

AF XY:

0.0872

AC XY:

6490

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.0785

Gnomad4 ASJ

AF:

0.0424

Gnomad4 EAS

AF:

0.0401

Gnomad4 SAS

AF:

0.0243

Gnomad4 FIN

AF:

0.0138

Gnomad4 NFE

AF:

0.0269

Gnomad4 OTH

AF:

0.0707

Alfa

AF:

0.0566

Hom.:

286

Bravo

AF:

0.103

Asia WGS

AF:

0.0700

AC:

244

AN:

3478

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 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.83

DANN

Benign

0.74

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