Variant chr10-80603648-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001388272.1(SH2D4B):c.713A>G(p.His238Arg) variant causes a missense change. The variant allele was found at a frequency of 0.27 in 1,602,382 control chromosomes in the GnomAD database, including 62,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8445 hom., cov: 33)

Exomes 𝑓: 0.26 ( 53936 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92

Variant links:

Genes affected

SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH2D4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018744469).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D4B	NM_001388272.1 linkuse as main transcript	c.713A>G	p.His238Arg	missense_variant	5/8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2 linkuse as main transcript	c.713A>G	p.His238Arg	missense_variant	5/7		NP_997255.2	Q5SQS7-2
SH2D4B	NM_001145719.1 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	5/7		NP_001139191.1	Q5SQS7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SH2D4B	ENST00000646907.2 linkuse as main transcript	c.713A>G	p.His238Arg	missense_variant	5/8		NM_001388272.1	ENSP00000494732.1	A0A2R8Y5Q0
SH2D4B	ENST00000339284.6 linkuse as main transcript	c.713A>G	p.His238Arg	missense_variant	5/7	2		ENSP00000345295.2	Q5SQS7-2
SH2D4B	ENST00000313455.5 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	5/7	2		ENSP00000314242.4	Q5SQS7-3

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48666

AN:

151932

Hom.:

8426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.297

AC:

67986

AN:

228966

Hom.:

10687

AF XY:

0.292

AC XY:

36237

AN XY:

123966

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.496

Gnomad SAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.264

AC:

383232

AN:

1450332

Hom.:

53936

Cov.:

AF XY:

0.265

AC XY:

190542

AN XY:

720308

show subpopulations

Gnomad4 AFR exome

AF:

0.451

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.314

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.321

AC:

48738

AN:

152050

Hom.:

8445

Cov.:

AF XY:

0.321

AC XY:

23877

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.516

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.286

Hom.:

3227

Bravo

AF:

0.326

TwinsUK

AF:

0.246

AC:

912

ALSPAC

AF:

0.252

AC:

970

ESP6500AA

AF:

0.433

AC:

1903

ESP6500EA

AF:

0.257

AC:

2206

ExAC

AF:

0.287

AC:

34732

Asia WGS

AF:

0.394

AC:

1367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.65

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.11

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Uncertain

0.59

PROVEAN

Benign

3.9

N;.;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0

B;.;B

Vest4

0.055

MPC

0.18

ClinPred

0.0045

GERP RS

6.0

gMVP

0.34

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over