rs155103

Positions:

• chr2-181486016-A-G
• chr2-181486016-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.1153+24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 1,563,114 control chromosomes in the GnomAD database, including 457,531 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 (43632 hom., cov: 32)
  • Exomes 𝑓: 0.76 (413899 hom.)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6	c.1153+24A>G		intron_variant		ENST00000397033.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7	c.1153+24A>G		intron_variant		1	NM_000885.6	P1
ITGA4	ENST00000233573.6	c.1153+24A>G		intron_variant		1
ITGA4	ENST00000465522.5	n.1428A>G		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114758 AN: 151990 Hom.: 43596 Cov.: 32

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.761

GnomAD3 exomes AF: 0.749 AC: 157581 AN: 210274 Hom.: 59483 AF XY: 0.745 AC XY: 85942 AN XY: 115334

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.789

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.636

Gnomad SAS exome AF: 0.622

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.782

Gnomad OTH exome AF: 0.770

GnomAD4 exome AF: 0.764 AC: 1078495 AN: 1411006 Hom.: 413899 Cov.: 34 AF XY: 0.761 AC XY: 531950 AN XY: 699410

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.770

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.757

GnomAD4 genome AF: 0.755 AC: 114846 AN: 152108 Hom.: 43632 Cov.: 32 AF XY: 0.751 AC XY: 55846 AN XY: 74338

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.762

Alfa AF: 0.746 Hom.: 6112

Bravo AF: 0.758

Asia WGS AF: 0.638 AC: 2222 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.68

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: rs155103; hg19: chr2-182350743;