NM_002208.5:c.3445-62G>A

Variant names:

• chr17-3715004-C-T
• rs1367950
• NM_002208.5:c.3445-62G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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]

P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ITGAE	NM_002208.5	c.3445-62G>A		intron_variant	Intron 30 of 30	ENST00000263087.9	NP_002199.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAE	ENST00000263087.9	c.3445-62G>A		intron_variant	Intron 30 of 30	1	NM_002208.5	ENSP00000263087.4

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

African (AFR) AF: 0.128 AC: 2692 AN: 20990

American (AMR) AF: 0.245 AC: 9381 AN: 38256

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 10426 AN: 21150

East Asian (EAS) AF: 0.408 AC: 14949 AN: 36624

South Asian (SAS) AF: 0.587 AC: 41307 AN: 70398

European-Finnish (FIN) AF: 0.446 AC: 17177 AN: 38518

Middle Eastern (MID) AF: 0.547 AC: 2454 AN: 4484

European-Non Finnish (NFE) AF: 0.496 AC: 272985 AN: 549950

Other (OTH) AF: 0.460 AC: 18063 AN: 39230

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

African (AFR) AF: 0.144 AC: 5968 AN: 41516

American (AMR) AF: 0.326 AC: 4983 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1803 AN: 5168

South Asian (SAS) AF: 0.598 AC: 2887 AN: 4826

European-Finnish (FIN) AF: 0.446 AC: 4710 AN: 10570

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 34021 AN: 67976

Other (OTH) AF: 0.417 AC: 881 AN: 2114

Alfa AF: 0.466 Hom.: 29147

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
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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