rs155101

chr2-181485418-G-Achr2-181485418-G-Cchr2-181485418-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	UniProt
ITGA4	NM_000885.6	c.1042-463G>A		intron_variant		ENST00000397033.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7	c.1042-463G>A		intron_variant		1	NM_000885.6	P1
ITGA4	ENST00000233573.6	c.1042-463G>A		intron_variant		1
ITGA4	ENST00000465522.5	n.1293-463G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.762

Alfa AF: 0.697 Hom.: 2061

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

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: rs155101; hg19: chr2-182350145;