Variant chr17-3732446-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000263087.9(ITGAE):c.2676G>C(p.Gln892His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 1,613,628 control chromosomes in the GnomAD database, including 4,012 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 0.080 ( 674 hom., cov: 32)

Exomes 𝑓: 0.058 ( 3338 hom. )

Consequence

ITGAE
ENST00000263087.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.798

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019013882).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 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.2676G>C	p.Gln892His	missense_variant	22/31	ENST00000263087.9	NP_002199.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ITGAE	ENST00000263087.9 linkuse as main transcript	c.2676G>C	p.Gln892His	missense_variant	22/31	1	NM_002208.5	ENSP00000263087	P1
ITGAE	ENST00000574026.2 linkuse as main transcript	c.260-1263G>C		intron_variant		3		ENSP00000467977
ITGAE	ENST00000571185.1 linkuse as main transcript	n.247G>C		non_coding_transcript_exon_variant	3/7	3

Frequencies

GnomAD3 genomes

AF:

0.0805

AC:

12244

AN:

152146

Hom.:

673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.0982

Gnomad EAS

AF:

0.0310

Gnomad SAS

AF:

0.0364

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0530

Gnomad OTH

AF:

0.0842

GnomAD3 exomes

AF:

0.0796

AC:

20003

AN:

251448

Hom.:

1315

AF XY:

0.0712

AC XY:

9683

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.0993

Gnomad EAS exome

AF:

0.0284

Gnomad SAS exome

AF:

0.0351

Gnomad FIN exome

AF:

0.0765

Gnomad NFE exome

AF:

0.0529

Gnomad OTH exome

AF:

0.0761

GnomAD4 exome

AF:

0.0575

AC:

84072

AN:

1461364

Hom.:

3338

Cov.:

AF XY:

0.0559

AC XY:

40675

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0268

Gnomad4 SAS exome

AF:

0.0354

Gnomad4 FIN exome

AF:

0.0750

Gnomad4 NFE exome

AF:

0.0501

Gnomad4 OTH exome

AF:

0.0640

GnomAD4 genome

AF:

0.0805

AC:

12254

AN:

152264

Hom.:

674

Cov.:

AF XY:

0.0813

AC XY:

6049

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.0982

Gnomad4 EAS

AF:

0.0306

Gnomad4 SAS

AF:

0.0364

Gnomad4 FIN

AF:

0.0779

Gnomad4 NFE

AF:

0.0530

Gnomad4 OTH

AF:

0.0838

Alfa

AF:

0.0521

Hom.:

208

Bravo

AF:

0.0893

TwinsUK

AF:

0.0437

AC:

162

ALSPAC

AF:

0.0426

AC:

164

ESP6500AA

AF:

0.0962

AC:

424

ESP6500EA

AF:

0.0526

AC:

452

ExAC

AF:

0.0732

AC:

8890

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

EpiCase

AF:

0.0547

EpiControl

AF:

0.0550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.69

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.13

Sift

Benign

0.036

Sift4G

Uncertain

0.056

Polyphen

0.99

Vest4

0.059

MutPred

0.28

Loss of sheet (P = 0.0817);

MPC

0.25

ClinPred

0.017

GERP RS

5.1

Varity_R

0.30

gMVP

0.28

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