rs220479

Positions:

• chr17-3753881-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002208.5(ITGAE):​c.1429A>G​(p.Ile477Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 1,613,688 control chromosomes in the GnomAD database, including 515,181 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.82 (52670 hom., cov: 33)
  • Exomes 𝑓: 0.79 (462511 hom.)
• Consequence: ITGAE NM_002208.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5543226E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAE	NM_002208.5	c.1429A>G	p.Ile477Val	missense_variant	13/31	ENST00000263087.9	NP_002199.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAE	ENST00000263087.9	c.1429A>G	p.Ile477Val	missense_variant	13/31	1	NM_002208.5	ENSP00000263087.4
ITGAE	ENST00000572121.1	n.110A>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124917 AN: 151916 Hom.: 52615 Cov.: 33

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.794

GnomAD3 exomes AF: 0.729 AC: 182961 AN: 251106 Hom.: 69937 AF XY: 0.723 AC XY: 98185 AN XY: 135732

Gnomad AFR exome AF: 0.967

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.761

Gnomad EAS exome AF: 0.377

Gnomad SAS exome AF: 0.555

Gnomad FIN exome AF: 0.854

Gnomad NFE exome AF: 0.817

Gnomad OTH exome AF: 0.757

GnomAD4 exome AF: 0.788 AC: 1152380 AN: 1461654 Hom.: 462511 Cov.: 58 AF XY: 0.781 AC XY: 567573 AN XY: 727146

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.761

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.553

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.821

Gnomad4 OTH exome AF: 0.776

GnomAD4 genome AF: 0.822 AC: 125034 AN: 152034 Hom.: 52670 Cov.: 33 AF XY: 0.813 AC XY: 60372 AN XY: 74282

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.793

Alfa AF: 0.807 Hom.: 43399

Bravo AF: 0.816

TwinsUK AF: 0.811 AC: 3008

ALSPAC AF: 0.815 AC: 3142

ESP6500AA AF: 0.956 AC: 4210

ESP6500EA AF: 0.817 AC: 7022

ExAC AF: 0.736 AC: 89309

Asia WGS AF: 0.522 AC: 1817 AN: 3478

EpiCase AF: 0.814

EpiControl AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.025
DANN	Benign	0.24
DEOGEN2	Benign	0.052	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.0040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.015
MPC		0.13
ClinPred		0.0036	T
GERP RS		-3.8
Varity_R		0.019
gMVP		0.64

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

Other links and lift over

dbSNP: rs220479; hg19: chr17-3657175; COSMIC: COSV53993148;