17-3732446-C-A

Variant names:

• chr17-3732446-C-A
• rs3744679
• NM_002208.5:c.2676G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002208.5(ITGAE):​c.2676G>T​(p.Gln892His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: ITGAE NM_002208.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• Publications: 19 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3049934).

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.2676G>T	p.Gln892His	missense	Exon 22 of 31	NP_002199.3
	ITGAE	NM_001425071.1		c.2676G>T	p.Gln892His	missense	Exon 22 of 30	NP_001412000.1
	ITGAE	NM_001425072.1		c.2676G>T	p.Gln892His	missense	Exon 22 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.2676G>T	p.Gln892His	missense	Exon 22 of 31	ENSP00000263087.4
	ITGAE	ENST00000571185.1	TSL:3	n.247G>T		non_coding_transcript_exon	Exon 3 of 7
	ITGAE	ENST00000574026.2	TSL:3	c.259-1263G>T		intron	N/A	ENSP00000467977.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.80
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Benign	0.036	D
Sift4G	Uncertain	0.056	T
Polyphen		0.99	D
Vest4		0.059
MutPred		0.28		Loss of sheet (P = 0.0817)
MVP		0.80
MPC		0.25
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.30
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3744679; hg19: chr17-3635740;