rs1038034

Positions:

• chr2-181492807-A-G

Variant summary

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

The NM_000885.6(ITGA4):​c.1154-518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,258 control chromosomes in the GnomAD database, including 1,294 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 (1294 hom., cov: 33)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA4	NM_000885.6	c.1154-518A>G		intron_variant		ENST00000397033.7	NP_000876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA4	ENST00000397033.7	c.1154-518A>G		intron_variant		1	NM_000885.6	ENSP00000380227	P1
ITGA4	ENST00000233573.6	c.1154-518A>G		intron_variant		1		ENSP00000233573

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17390 AN: 152140 Hom.: 1293 Cov.: 33

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0809

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17395 AN: 152258 Hom.: 1294 Cov.: 33 AF XY: 0.122 AC XY: 9094 AN XY: 74450

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.0594

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0834

Alfa AF: 0.123 Hom.: 239

Bravo AF: 0.106

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	20
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1038034; hg19: chr2-182357534;