17-3715004-C-T

Position:

• chr17-3715004-C-T

Variant summary

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

The NM_002208.5(ITGAE):​c.3445-62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 971,732 control chromosomes in the GnomAD database, including 110,105 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 0.38 (13045 hom., cov: 33)
  • Exomes 𝑓: 0.48 (97060 hom.)
• Consequence: ITGAE NM_002208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAE	NM_002208.5	c.3445-62G>A		intron_variant		ENST00000263087.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAE	ENST00000263087.9	c.3445-62G>A		intron_variant		1	NM_002208.5	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57641 AN: 152012 Hom.: 13057 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.475 AC: 389434 AN: 819600 Hom.: 97060 AF XY: 0.484 AC XY: 208794 AN XY: 431652

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.379 AC: 57634 AN: 152132 Hom.: 13045 Cov.: 33 AF XY: 0.381 AC XY: 28313 AN XY: 74360

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.417

Alfa AF: 0.482 Hom.: 24243

Bravo AF: 0.352

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.056
DANN	Benign	0.33

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: rs1367950; hg19: chr17-3618298; COSMIC: COSV53990892;