rs2124440

Variant names:

• chr2-181463487-G-A
• rs2124440
• NM_000885.6:c.319+5170G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-181463487-G-A
• chr2-181463487-G-C
• chr2-181463487-G-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+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
• Publications: 34 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000885.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA4	NM_000885.6	MANE Select	c.319+5170G>A		intron	N/A	NP_000876.3	P13612-1
	ITGA4	NM_001316312.2		c.319+5170G>A		intron	N/A	NP_001303241.1	P13612-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA4	ENST00000397033.7	TSL:1 MANE Select	c.319+5170G>A		intron	N/A	ENSP00000380227.2	P13612-1
	ITGA4	ENST00000233573.6	TSL:1	c.319+5170G>A		intron	N/A	ENSP00000233573.6	E7EP60
	ITGA4	ENST00000339307.8	TSL:1	c.319+5170G>A		intron	N/A	ENSP00000340149.4	P13612-2

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

African (AFR) AF: 0.573 AC: 23454 AN: 40918

American (AMR) AF: 0.540 AC: 8225 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1879 AN: 5168

South Asian (SAS) AF: 0.600 AC: 2893 AN: 4818

European-Finnish (FIN) AF: 0.581 AC: 6133 AN: 10550

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36879 AN: 67918

Other (OTH) AF: 0.538 AC: 1134 AN: 2106

Alfa AF: 0.541 Hom.: 42363

Bravo AF: 0.543

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.23
PhyloP100		0.63
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: rs2124440; hg19: chr2-182328214;