rs155101

Variant names:

• chr2-181485418-G-A
• rs155101
• NM_000885.6:c.1042-463G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-181485418-G-A
• chr2-181485418-G-C
• chr2-181485418-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000885.6(ITGA4):​c.1042-463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 150,920 control chromosomes in the GnomAD database, including 43,232 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 0.76 (43232 hom., cov: 27)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA4	NM_000885.6	c.1042-463G>A		intron_variant	Intron 9 of 27	ENST00000397033.7	NP_000876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA4	ENST00000397033.7	c.1042-463G>A		intron_variant	Intron 9 of 27	1	NM_000885.6	ENSP00000380227.2
ITGA4	ENST00000233573.6	c.1042-463G>A		intron_variant	Intron 9 of 15	1		ENSP00000233573.6
ITGA4	ENST00000465522.5	n.1293-463G>A		intron_variant	Intron 9 of 9	2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 113888 AN: 150810 Hom.: 43197 Cov.: 27

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.755 AC: 113973 AN: 150920 Hom.: 43232 Cov.: 27 AF XY: 0.752 AC XY: 55387 AN XY: 73666

African (AFR) AF: 0.720 AC: 29528 AN: 41016

American (AMR) AF: 0.794 AC: 12070 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2673 AN: 3464

East Asian (EAS) AF: 0.627 AC: 3205 AN: 5114

South Asian (SAS) AF: 0.615 AC: 2954 AN: 4802

European-Finnish (FIN) AF: 0.771 AC: 7917 AN: 10268

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 52980 AN: 67762

Other (OTH) AF: 0.762 AC: 1596 AN: 2094

Alfa AF: 0.697 Hom.: 2251

Bravo AF: 0.758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.67
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs155101; hg19: chr2-182350145;