17-3732446-C-G

Variant summary

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

The NM_002208.5(ITGAE):c.2676G>C(p.Gln892His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 1,613,628 control chromosomes in the GnomAD database, including 4,012 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.080 (674 hom., cov: 32)
  • Exomes 𝑓: 0.058 (3338 hom.)
• Consequence: ITGAE NM_002208.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

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 (MetaRNN=0.0019013882).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAE	NM_002208.5	c.2676G>C	p.Gln892His	missense_variant	22/31	ENST00000263087.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAE	ENST00000263087.9	c.2676G>C	p.Gln892His	missense_variant	22/31	1	NM_002208.5	P1
ITGAE	ENST00000574026.2	c.260-1263G>C		intron_variant		3
ITGAE	ENST00000571185.1	n.247G>C		non_coding_transcript_exon_variant	3/7	3

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12244 AN: 152146 Hom.: 673 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0842

GnomAD3 exomes AF: 0.0796 AC: 20003 AN: 251448 Hom.: 1315 AF XY: 0.0712 AC XY: 9683 AN XY: 135902

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.0993

Gnomad EAS exome AF: 0.0284

Gnomad SAS exome AF: 0.0351

Gnomad FIN exome AF: 0.0765

Gnomad NFE exome AF: 0.0529

Gnomad OTH exome AF: 0.0761

GnomAD4 exome AF: 0.0575 AC: 84072 AN: 1461364 Hom.: 3338 Cov.: 32 AF XY: 0.0559 AC XY: 40675 AN XY: 727046

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0268

Gnomad4 SAS exome AF: 0.0354

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.0501

Gnomad4 OTH exome AF: 0.0640

GnomAD4 genome AF: 0.0805 AC: 12254 AN: 152264 Hom.: 674 Cov.: 32 AF XY: 0.0813 AC XY: 6049 AN XY: 74434

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.0982

Gnomad4 EAS AF: 0.0306

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0838

Alfa AF: 0.0521 Hom.: 208

Bravo AF: 0.0893

TwinsUK AF: 0.0437 AC: 162

ALSPAC AF: 0.0426 AC: 164

ESP6500AA AF: 0.0962 AC: 424

ESP6500EA AF: 0.0526 AC: 452

ExAC AF: 0.0732 AC: 8890

Asia WGS AF: 0.0460 AC: 160 AN: 3478

EpiCase AF: 0.0547

EpiControl AF: 0.0550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.61	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	0.43	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.69	P
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);
MPC		0.25
ClinPred		0.017	T
GERP RS		5.1
Varity_R		0.30
gMVP		0.28

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: rs3744679; hg19: chr17-3635740; COSMIC: COSV53991013; COSMIC: COSV53991013;