rs220470

Positions:

• chr17-3761681-A-G

Variant summary

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

The NM_002208.5(ITGAE):​c.316-161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,142 control chromosomes in the GnomAD database, including 39,056 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 0.70 (39056 hom., cov: 33)
• Consequence: ITGAE NM_002208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAE	NM_002208.5	c.316-161T>C		intron_variant		ENST00000263087.9	NP_002199.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAE	ENST00000263087.9	c.316-161T>C		intron_variant		1	NM_002208.5	ENSP00000263087	P1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106960 AN: 152024 Hom.: 39027 Cov.: 33

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.704 AC: 107047 AN: 152142 Hom.: 39056 Cov.: 33 AF XY: 0.689 AC XY: 51229 AN XY: 74396

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.680

Alfa AF: 0.691 Hom.: 52416

Bravo AF: 0.704

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.6
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs220470; hg19: chr17-3664975; COSMIC: COSV53991710;