rs155095

chr2-181478551-A-Gchr2-181478551-A-T

Variant summary

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

The NM_000885.6(ITGA4):c.557-206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,836 control chromosomes in the GnomAD database, including 42,399 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 0.74 (42399 hom., cov: 31)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6	c.557-206A>G		intron_variant		ENST00000397033.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7	c.557-206A>G		intron_variant		1	NM_000885.6	P1
ITGA4	ENST00000233573.6	c.557-206A>G		intron_variant		1
ITGA4	ENST00000478440.1	n.185-206A>G		intron_variant, non_coding_transcript_variant		1
ITGA4	ENST00000465522.5	n.808-206A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112758 AN: 151718 Hom.: 42364 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.743 AC: 112842 AN: 151836 Hom.: 42399 Cov.: 31 AF XY: 0.741 AC XY: 54975 AN XY: 74208

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.767

Alfa AF: 0.757 Hom.: 5421

Bravo AF: 0.749

Asia WGS AF: 0.640 AC: 2229 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	11
Dann	Benign	0.84

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: rs155095; hg19: chr2-182343278;