GeneBe

rs374066058

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000885.6(ITGA4):​c.124C>G​(p.Leu42Val) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ITGA4
NM_000885.6 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.512

Publications

0 publications found
Variant links:
Genes affected
ITGA4 (HGNC:6140): (integrin subunit alpha 4) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15731362).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000885.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ITGA4
NM_000885.6
MANE Select
c.124C>Gp.Leu42Val
missense
Exon 1 of 28NP_000876.3P13612-1
ITGA4
NM_001316312.2
c.124C>Gp.Leu42Val
missense
Exon 1 of 5NP_001303241.1P13612-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ITGA4
ENST00000397033.7
TSL:1 MANE Select
c.124C>Gp.Leu42Val
missense
Exon 1 of 28ENSP00000380227.2P13612-1
ITGA4
ENST00000233573.6
TSL:1
c.124C>Gp.Leu42Val
missense
Exon 1 of 16ENSP00000233573.6E7EP60
ITGA4
ENST00000339307.8
TSL:1
c.124C>Gp.Leu42Val
missense
Exon 1 of 5ENSP00000340149.4P13612-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000240
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Uncertain
0.038
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
1.4
L
PhyloP100
0.51
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.28
N
REVEL
Benign
0.23
Sift
Benign
0.41
T
Sift4G
Benign
0.45
T
Polyphen
0.82
P
Vest4
0.25
MVP
0.83
MPC
0.53
ClinPred
0.20
T
GERP RS
3.6
PromoterAI
0.017
Neutral
Varity_R
0.18
gMVP
0.69
Mutation Taster
=72/28
polymorphism

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

Other links and lift over

dbSNP: rs374066058; hg19: chr2-182322505; API