2-181486016-A-G

Variant names:

• chr2-181486016-A-G
• rs155103
• NM_000885.6:c.1153+24A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.83).
• 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 rank	MANE	Protein	UniProt
ITGA4	NM_000885.6	c.1153+24A>G		intron_variant	Intron 10 of 27	ENST00000397033.7	NP_000876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA4	ENST00000397033.7	c.1153+24A>G		intron_variant	Intron 10 of 27	1	NM_000885.6	ENSP00000380227.2
ITGA4	ENST00000233573.6	c.1153+24A>G		intron_variant	Intron 10 of 15	1		ENSP00000233573.6
ITGA4	ENST00000465522.5	n.1428A>G		non_coding_transcript_exon_variant	Exon 10 of 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

GnomAD2 exomes AF: 0.749 AC: 157581 AN: 210274 AF XY: 0.745

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 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

African (AFR) AF: 0.716 AC: 21763 AN: 30406

American (AMR) AF: 0.786 AC: 24782 AN: 31528

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 19143 AN: 24570

East Asian (EAS) AF: 0.618 AC: 23095 AN: 37342

South Asian (SAS) AF: 0.619 AC: 48349 AN: 78068

European-Finnish (FIN) AF: 0.770 AC: 40768 AN: 52924

Middle Eastern (MID) AF: 0.764 AC: 4291 AN: 5616

European-Non Finnish (NFE) AF: 0.780 AC: 852223 AN: 1092288

Other (OTH) AF: 0.757 AC: 44081 AN: 58264

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

African (AFR) AF: 0.720 AC: 29873 AN: 41476

American (AMR) AF: 0.794 AC: 12150 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2680 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3236 AN: 5160

South Asian (SAS) AF: 0.614 AC: 2965 AN: 4828

European-Finnish (FIN) AF: 0.767 AC: 8104 AN: 10570

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53176 AN: 67990

Other (OTH) AF: 0.762 AC: 1610 AN: 2114

Alfa AF: 0.744 Hom.: 6298

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
PhyloP100		0.14
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: rs155103; hg19: chr2-182350743;