Variant 16-28871920-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387430.1(SH2B1):c.1450A>T(p.Thr484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 146,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T484A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH2B1
NM_001387430.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.432

Variant links:

Genes affected

SH2B1 (HGNC:30417): (SH2B adaptor protein 1) This gene encodes a member of the SH2-domain containing mediators family. The encoded protein mediates activation of various kinases and may function in cytokine and growth factor receptor signaling and cellular transformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

SH2B1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026253998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2B1	NM_001387430.1 linkuse as main transcript	c.1450A>T	p.Thr484Ser	missense_variant	5/8	ENST00000684370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2B1	ENST00000684370.1 linkuse as main transcript	c.1450A>T	p.Thr484Ser	missense_variant	5/8		NM_001387430.1	P3	Q9NRF2-1

Frequencies

GnomAD3 genomes

AF:

0.00000684

AC:

AN:

146200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000213

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1423016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709210

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000684

AC:

AN:

146200

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71184

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000213

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.053

T;.;T;T;.;T;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.21

M_CAP

Benign

0.014

MetaRNN

Benign

0.026

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;.;N;N;.;N;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.51

N;N;N;.;N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.55

T;T;T;.;T;T;T;T

Sift4G

Benign

0.87

T;T;T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B;B;.

Vest4

0.13

MutPred

0.22

Gain of glycosylation at T484 (P = 0.0774);Gain of glycosylation at T484 (P = 0.0774);.;Gain of glycosylation at T484 (P = 0.0774);Gain of glycosylation at T484 (P = 0.0774);.;Gain of glycosylation at T484 (P = 0.0774);.;

MVP

0.10

MPC

0.21

ClinPred

0.020

GERP RS

3.1

Varity_R

0.022

gMVP

0.091

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