chr2-181485360-T-A

Position:

• chr2-181485360-T-A

Variant summary

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

The NM_000885.6(ITGA4):​c.1042-521T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,766 control chromosomes in the GnomAD database, including 26,105 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 0.59 (26105 hom., cov: 30)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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]

ITGA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA4	NM_000885.6	c.1042-521T>A		intron_variant		ENST00000397033.7	NP_000876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA4	ENST00000397033.7	c.1042-521T>A		intron_variant		1	NM_000885.6	ENSP00000380227.2
ITGA4	ENST00000233573.6	c.1042-521T>A		intron_variant		1		ENSP00000233573.6
ITGA4	ENST00000465522.5	n.1293-521T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88856 AN: 151648 Hom.: 26085 Cov.: 30

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.586 AC: 88922 AN: 151766 Hom.: 26105 Cov.: 30 AF XY: 0.585 AC XY: 43348 AN XY: 74128

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.584

Alfa AF: 0.479 Hom.: 1436

Bravo AF: 0.592

Asia WGS AF: 0.471 AC: 1642 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.56

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: rs155100; hg19: chr2-182350087;