rs1716

Variant names:

• chr17-3729542-G-A
• rs1716
• NM_002208.5:c.2848C>T

Variant summary

Our verdict is Benign. The variant received -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.

• Frequency:
  • Genomes: 𝑓 0.26 (6309 hom., cov: 32)
  • Exomes 𝑓: 0.34 (85299 hom.)
• Consequence: ITGAE NM_002208.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 43 publications found

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]

ENSG00000262358 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002208.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAE	NM_002208.5	MANE Select	c.2848C>T	p.Arg950Trp	missense	Exon 24 of 31	NP_002199.3
	ITGAE	NM_001425072.1		c.2848C>T	p.Arg950Trp	missense	Exon 24 of 29	NP_001412001.1
	ITGAE	NM_001425071.1		c.2835-1374C>T		intron	N/A	NP_001412000.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.2848C>T	p.Arg950Trp	missense	Exon 24 of 31	ENSP00000263087.4
	ENSG00000262358	ENST00000575043.1	TSL:2	n.182G>A		non_coding_transcript_exon	Exon 1 of 2
	ITGAE	ENST00000574026.2	TSL:3	c.339-1374C>T		intron	N/A	ENSP00000467977.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39360 AN: 150674 Hom.: 6309 Cov.: 32

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

GnomAD2 exomes AF: 0.312 AC: 78559 AN: 251478 AF XY: 0.331

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 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.: 28 AF XY: 0.342 AC XY: 245353 AN XY: 716584

African (AFR) AF: 0.0797 AC: 2648 AN: 33218

American (AMR) AF: 0.147 AC: 6590 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8181 AN: 25978

East Asian (EAS) AF: 0.337 AC: 13326 AN: 39544

South Asian (SAS) AF: 0.502 AC: 43006 AN: 85612

European-Finnish (FIN) AF: 0.358 AC: 19119 AN: 53388

Middle Eastern (MID) AF: 0.379 AC: 2169 AN: 5722

European-Non Finnish (NFE) AF: 0.337 AC: 367704 AN: 1089834

Other (OTH) AF: 0.329 AC: 19592 AN: 59604

GnomAD4 genome AF: 0.261 AC: 39361 AN: 150788 Hom.: 6309 Cov.: 32 AF XY: 0.268 AC XY: 19772 AN XY: 73740

African (AFR) AF: 0.0924 AC: 3779 AN: 40884

American (AMR) AF: 0.195 AC: 2953 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1112 AN: 3458

East Asian (EAS) AF: 0.308 AC: 1569 AN: 5094

South Asian (SAS) AF: 0.517 AC: 2476 AN: 4788

European-Finnish (FIN) AF: 0.362 AC: 3807 AN: 10530

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.336 AC: 22748 AN: 67602

Other (OTH) AF: 0.250 AC: 522 AN: 2088

Alfa AF: 0.312 Hom.: 36754

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.00040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.16
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.048
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.043
MPC		0.62
ClinPred		0.025	T
GERP RS		-0.31
Varity_R		0.20
gMVP		0.26
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1716; hg19: chr17-3632836; COSMIC: COSV53992126; COSMIC: COSV53992126;