Variant rs1716 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002208.5(ITGAE):c.2848C>T(p.Arg950Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,588,368 control chromosomes in the GnomAD database, including 91,608 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 6309 hom., cov: 32)

Exomes 𝑓: 0.34 ( 85299 hom. )

Consequence

ITGAE
NM_002208.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158

Variant links:

Genes affected

ITGAE (HGNC:6147): (integrin subunit alpha E) Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an I-domain-containing alpha integrin that undergoes post-translational cleavage in the extracellular domain, yielding disulfide-linked heavy and light chains. In combination with the beta 7 integrin, this protein forms the E-cadherin binding integrin known as the human mucosal lymphocyte-1 antigen. This protein is preferentially expressed in human intestinal intraepithelial lymphocytes (IEL), and in addition to a role in adhesion, it may serve as an accessory molecule for IEL activation. [provided by RefSeq, Jul 2008]

ITGAE links:

ITGAE (HGNC:):

ITGAE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) 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
ITGAE	NM_002208.5 linkuse as main transcript	c.2848C>T	p.Arg950Trp	missense_variant	24/31	ENST00000263087.9	NP_002199.3	P38570

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITGAE	ENST00000263087.9 linkuse as main transcript	c.2848C>T	p.Arg950Trp	missense_variant	24/31	1	NM_002208.5	ENSP00000263087.4	P38570
ITGAE	ENST00000574026.2 linkuse as main transcript	c.339-1374C>T		intron_variant		3		ENSP00000467977.1	K7EQU0
ENSG00000262358	ENST00000575043.1 linkuse as main transcript	n.182G>A		non_coding_transcript_exon_variant	1/2	2
ITGAE	ENST00000571185.1 linkuse as main transcript	n.406-1374C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39360

AN:

150674

Hom.:

6309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0923

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.518

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.251

GnomAD3 exomes

AF:

0.312

AC:

78559

AN:

251478

Hom.:

13941

AF XY:

0.331

AC XY:

45024

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0853

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.312

Gnomad SAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.356

Gnomad NFE exome

AF:

0.336

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.336

AC:

482335

AN:

1437580

Hom.:

85299

Cov.:

AF XY:

0.342

AC XY:

245353

AN XY:

716584

show subpopulations

Gnomad4 AFR exome

AF:

0.0797

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.502

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.261

AC:

39361

AN:

150788

Hom.:

6309

Cov.:

AF XY:

0.268

AC XY:

19772

AN XY:

73740

show subpopulations

Gnomad4 AFR

AF:

0.0924

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.517

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.321

Hom.:

20437

Bravo

AF:

0.233

TwinsUK

AF:

0.345

AC:

1281

ALSPAC

AF:

0.334

AC:

1288

ESP6500AA

AF:

0.0946

AC:

417

ESP6500EA

AF:

0.334

AC:

2871

ExAC

AF:

0.317

AC:

38510

Asia WGS

AF:

0.408

AC:

1421

AN:

3478

EpiCase

AF:

0.337

EpiControl

AF:

0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.61

MetaRNN

Benign

0.00040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.048

Sift

Uncertain

0.013

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.043

MPC

0.62

ClinPred

0.025

GERP RS

-0.31

Varity_R

0.20

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: 13

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