rs2124440

chr2-181463487-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+5170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,384 control chromosomes in the GnomAD database, including 22,974 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 0.55 (22974 hom., cov: 31)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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 (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6	c.319+5170G>A		intron_variant		ENST00000397033.7
ITGA4	NM_001316312.2	c.319+5170G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7	c.319+5170G>A		intron_variant		1	NM_000885.6	P1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 82898 AN: 151270 Hom.: 22955 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.548 AC: 82961 AN: 151384 Hom.: 22974 Cov.: 31 AF XY: 0.550 AC XY: 40700 AN XY: 73990

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.538

Alfa AF: 0.544 Hom.: 11498

Bravo AF: 0.543

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.5
Dann	Benign	0.23

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: rs2124440; hg19: chr2-182328214;