Variant rs17107368 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.900T>A(p.Asp300Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,990 control chromosomes in the GnomAD database, including 23,937 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 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 0.14 ( 1990 hom., cov: 31)

Exomes 𝑓: 0.17 ( 21947 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

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:

SH2D4B (HGNC:):

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=0.003282398).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 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.900T>A	p.Asp300Glu	missense_variant	6/8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2 linkuse as main transcript	c.897T>A	p.Asp299Glu	missense_variant	6/7		NP_997255.2	Q5SQS7-2
SH2D4B	NM_001145719.1 linkuse as main transcript	c.753T>A	p.Asp251Glu	missense_variant	6/7		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.900T>A	p.Asp300Glu	missense_variant	6/8		NM_001388272.1	ENSP00000494732.1	A0A2R8Y5Q0
SH2D4B	ENST00000339284.6 linkuse as main transcript	c.897T>A	p.Asp299Glu	missense_variant	6/7	2		ENSP00000345295.2	Q5SQS7-2
SH2D4B	ENST00000313455.5 linkuse as main transcript	c.753T>A	p.Asp251Glu	missense_variant	6/7	2		ENSP00000314242.4	Q5SQS7-3
SH2D4B	ENST00000372150.7 linkuse as main transcript	n.242T>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21554

AN:

152056

Hom.:

1992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0476

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.172

AC:

43286

AN:

251404

Hom.:

4276

AF XY:

0.171

AC XY:

23240

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.369

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.167

AC:

243889

AN:

1461816

Hom.:

21947

Cov.:

AF XY:

0.166

AC XY:

120431

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0445

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.398

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.142

AC:

21543

AN:

152174

Hom.:

1990

Cov.:

AF XY:

0.145

AC XY:

10798

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0476

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.172

Hom.:

1754

Bravo

AF:

0.136

TwinsUK

AF:

0.171

AC:

634

ALSPAC

AF:

0.153

AC:

589

ESP6500AA

AF:

0.0533

AC:

235

ESP6500EA

AF:

0.170

AC:

1463

ExAC

AF:

0.169

AC:

20519

Asia WGS

AF:

0.222

AC:

771

AN:

3478

EpiCase

AF:

0.170

EpiControl

AF:

0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.7

DANN

Benign

0.74

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.5

N;.;N

REVEL

Benign

0.014

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0010

B;.;B

Vest4

0.023

MPC

0.14

ClinPred

0.00077

GERP RS

-6.9

gMVP

0.11

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