2-181461180-C-T

Variant names:

• chr2-181461180-C-T
• rs3770138
• NM_000885.6:c.319+2863C>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.319+2863C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 146,808 control chromosomes in the GnomAD database, including 2,013 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 0.15 (2013 hom., cov: 25)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA4	NM_000885.6	c.319+2863C>T		intron_variant	Intron 2 of 27	ENST00000397033.7	NP_000876.3
ITGA4	NM_001316312.2	c.319+2863C>T		intron_variant	Intron 2 of 4		NP_001303241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA4	ENST00000397033.7	c.319+2863C>T		intron_variant	Intron 2 of 27	1	NM_000885.6	ENSP00000380227.2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22331 AN: 146690 Hom.: 2007 Cov.: 25

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.152 AC: 22353 AN: 146808 Hom.: 2013 Cov.: 25 AF XY: 0.153 AC XY: 10851 AN XY: 71140

African (AFR) AF: 0.0628 AC: 2486 AN: 39558

American (AMR) AF: 0.123 AC: 1785 AN: 14522

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 907 AN: 3424

East Asian (EAS) AF: 0.204 AC: 1021 AN: 4998

South Asian (SAS) AF: 0.155 AC: 683 AN: 4414

European-Finnish (FIN) AF: 0.203 AC: 2007 AN: 9870

Middle Eastern (MID) AF: 0.240 AC: 69 AN: 288

European-Non Finnish (NFE) AF: 0.191 AC: 12762 AN: 66838

Other (OTH) AF: 0.166 AC: 333 AN: 2004

Alfa AF: 0.178 Hom.: 7069

Bravo AF: 0.144

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.7
DANN	Benign	0.69
PhyloP100		0.93
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: rs3770138; hg19: chr2-182325907;