Variant chr2-181495455-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000885.6(ITGA4):c.1385+39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,478,834 control chromosomes in the GnomAD database, including 13,768 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 0.11 ( 1187 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12581 hom. )

Consequence

ITGA4
NM_000885.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.551

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]

ITGA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6 linkuse as main transcript	c.1385+39T>C		intron_variant		ENST00000397033.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7 linkuse as main transcript	c.1385+39T>C	intron_variant	1	NM_000885.6	P1	P13612-1
ITGA4	ENST00000233573.6 linkuse as main transcript	c.1385+39T>C	intron_variant	1
ITGA4	ENST00000473002.1 linkuse as main transcript	n.523+39T>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16289

AN:

152048

Hom.:

1183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.155

AC:

38451

AN:

247900

Hom.:

3613

AF XY:

0.155

AC XY:

20839

AN XY:

134526

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.0979

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.128

AC:

169898

AN:

1326670

Hom.:

12581

Cov.:

AF XY:

0.131

AC XY:

87182

AN XY:

667574

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.0963

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.107

AC:

16300

AN:

152164

Hom.:

1187

Cov.:

AF XY:

0.110

AC XY:

8165

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0262

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.122

Hom.:

1779

Bravo

AF:

0.109

Asia WGS

AF:

0.233

AC:

812

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.4

DANN

Benign

0.56

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over