rs155102

Positions:

• chr2-181485720-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_000885.6(ITGA4):​c.1042-161A>G 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 152,066 control chromosomes in the GnomAD database, including 26,156 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 (26156 hom., cov: 33)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6	c.1042-161A>G		intron_variant		ENST00000397033.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7	c.1042-161A>G		intron_variant		1	NM_000885.6	P1
ITGA4	ENST00000233573.6	c.1042-161A>G		intron_variant		1
ITGA4	ENST00000465522.5	n.1293-161A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89028 AN: 151948 Hom.: 26138 Cov.: 33

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.497

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: 89091 AN: 152066 Hom.: 26156 Cov.: 33 AF XY: 0.585 AC XY: 43469 AN XY: 74330

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.584

Alfa AF: 0.583 Hom.: 8076

Bravo AF: 0.591

Asia WGS AF: 0.471 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.86

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: rs155102; hg19: chr2-182350447; COSMIC: COSV52004459;