2-181459039-G-A

Position:

• chr2-181459039-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000885.6(ITGA4):​c.319+722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,070 control chromosomes in the GnomAD database, including 23,926 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 0.56 (23919 hom., cov: 32)
  • Exomes 𝑓: 0.44 (7 hom.)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6	c.319+722G>A		intron_variant		ENST00000397033.7
ITGA4	NM_001316312.2	c.319+722G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7	c.319+722G>A		intron_variant		1	NM_000885.6	P1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84537 AN: 151886 Hom.: 23901 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.439 AC: 29 AN: 66 Hom.: 7 Cov.: 0 AF XY: 0.464 AC XY: 13 AN XY: 28

Gnomad4 AMR exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.448

GnomAD4 genome AF: 0.557 AC: 84597 AN: 152004 Hom.: 23919 Cov.: 32 AF XY: 0.560 AC XY: 41632 AN XY: 74288

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.539

Alfa AF: 0.558 Hom.: 3105

Bravo AF: 0.550

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.54

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: rs1375493; hg19: chr2-182323766;