rs12988934

chr2-181458938-C-T

Variant summary

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

The NM_000885.6(ITGA4):c.319+621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 152,368 control chromosomes in the GnomAD database, including 640 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 0.064 (640 hom., cov: 32)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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 (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6	c.319+621C>T		intron_variant		ENST00000397033.7
ITGA4	NM_001316312.2	c.319+621C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7	c.319+621C>T		intron_variant		1	NM_000885.6	P1

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9692 AN: 152114 Hom.: 641 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.0570

GnomAD4 exome AF: 0.0368 AC: 5 AN: 136 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 3 AN XY: 78

Gnomad4 AMR exome AF: 0.0500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.125

Gnomad4 NFE exome AF: 0.0189

GnomAD4 genome AF: 0.0637 AC: 9690 AN: 152232 Hom.: 640 Cov.: 32 AF XY: 0.0703 AC XY: 5229 AN XY: 74430

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0624

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0681 Hom.: 746

Bravo AF: 0.0517

Asia WGS AF: 0.221 AC: 769 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	3.6
Dann	Benign	0.78

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: rs12988934; hg19: chr2-182323665;