17-3751686-A-G

Variant names:

• chr17-3751686-A-G
• rs11652878
• NM_002208.5:c.1857T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002208.5(ITGAE):​c.1857T>C​(p.Asn619Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,798 control chromosomes in the GnomAD database, including 11,366 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 0.13 (1457 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9909 hom.)
• Consequence: ITGAE NM_002208.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 21 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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.1857T>C	p.Asn619Asn	synonymous	Exon 15 of 31	NP_002199.3
	ITGAE	NM_001425071.1		c.1857T>C	p.Asn619Asn	synonymous	Exon 15 of 30	NP_001412000.1
	ITGAE	NM_001425072.1		c.1857T>C	p.Asn619Asn	synonymous	Exon 15 of 29	NP_001412001.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.1857T>C	p.Asn619Asn	synonymous	Exon 15 of 31	ENSP00000263087.4
	ITGAE	ENST00000572121.1	TSL:5	n.*184T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19873 AN: 151916 Hom.: 1441 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0970

Gnomad OTH AF: 0.119

GnomAD2 exomes AF: 0.124 AC: 31162 AN: 251380 AF XY: 0.124

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.0906

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.162

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.0987

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.111 AC: 161907 AN: 1461764 Hom.: 9909 Cov.: 32 AF XY: 0.112 AC XY: 81725 AN XY: 727198

African (AFR) AF: 0.169 AC: 5669 AN: 33478

American (AMR) AF: 0.0904 AC: 4044 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3660 AN: 26126

East Asian (EAS) AF: 0.218 AC: 8660 AN: 39698

South Asian (SAS) AF: 0.159 AC: 13738 AN: 86256

European-Finnish (FIN) AF: 0.189 AC: 10109 AN: 53420

Middle Eastern (MID) AF: 0.155 AC: 893 AN: 5768

European-Non Finnish (NFE) AF: 0.0973 AC: 108157 AN: 1111918

Other (OTH) AF: 0.116 AC: 6977 AN: 60388

GnomAD4 genome AF: 0.131 AC: 19926 AN: 152034 Hom.: 1457 Cov.: 31 AF XY: 0.136 AC XY: 10130 AN XY: 74316

African (AFR) AF: 0.171 AC: 7084 AN: 41474

American (AMR) AF: 0.108 AC: 1646 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3470

East Asian (EAS) AF: 0.170 AC: 878 AN: 5168

South Asian (SAS) AF: 0.155 AC: 749 AN: 4818

European-Finnish (FIN) AF: 0.197 AC: 2085 AN: 10602

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0969 AC: 6583 AN: 67920

Other (OTH) AF: 0.121 AC: 255 AN: 2110

Alfa AF: 0.109 Hom.: 3005

Bravo AF: 0.125

Asia WGS AF: 0.146 AC: 509 AN: 3478

EpiCase AF: 0.0974

EpiControl AF: 0.0988

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.031
DANN	Benign	0.30
PhyloP100		-1.1
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: rs11652878; hg19: chr17-3654980; COSMIC: COSV53990969; COSMIC: COSV53990969;