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GeneBe

17-3723726-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002208.5(ITGAE):c.3103T>C(p.Trp1035Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ITGAE
NM_002208.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.482
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15043986).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITGAENM_002208.5 linkuse as main transcriptc.3103T>C p.Trp1035Arg missense_variant 27/31 ENST00000263087.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGAEENST00000263087.9 linkuse as main transcriptc.3103T>C p.Trp1035Arg missense_variant 27/311 NM_002208.5 P1
ITGAEENST00000572179.5 linkuse as main transcriptn.112T>C non_coding_transcript_exon_variant 1/41
ITGAEENST00000570360.1 linkuse as main transcriptn.129T>C non_coding_transcript_exon_variant 1/52
ITGAEENST00000570415.5 linkuse as main transcriptn.497T>C non_coding_transcript_exon_variant 3/73

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000430
AC:
1
AN:
232538
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
127044
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000576
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1454110
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
722810
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 17, 2021The c.3103T>C (p.W1035R) alteration is located in exon 27 (coding exon 27) of the ITGAE gene. This alteration results from a T to C substitution at nucleotide position 3103, causing the tryptophan (W) at amino acid position 1035 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
6.2
Dann
Benign
0.48
DEOGEN2
Benign
0.055
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0058
N
LIST_S2
Benign
0.14
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.34
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
0.34
N
REVEL
Benign
0.14
Sift
Benign
0.42
T
Sift4G
Benign
0.66
T
Polyphen
0.0
B
Vest4
0.054
MutPred
0.75
Gain of disorder (P = 0.0017);
MVP
0.25
MPC
0.27
ClinPred
0.030
T
GERP RS
-1.3
Varity_R
0.044
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759382807; hg19: chr17-3627020; API