rs155102

Variant names:

• chr2-181485720-A-G
• rs155102
• NM_000885.6:c.1042-161A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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.

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.1042-161A>G		intron	N/A	NP_000876.3	P13612-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA4	ENST00000397033.7	TSL:1 MANE Select	c.1042-161A>G		intron	N/A	ENSP00000380227.2	P13612-1
	ITGA4	ENST00000233573.6	TSL:1	c.1042-161A>G		intron	N/A	ENSP00000233573.6	E7EP60
	ITGA4	ENST00000465522.5	TSL:2	n.1293-161A>G		intron	N/A

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

African (AFR) AF: 0.590 AC: 24437 AN: 41452

American (AMR) AF: 0.644 AC: 9850 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1858 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2602 AN: 5170

South Asian (SAS) AF: 0.454 AC: 2186 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6476 AN: 10562

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39793 AN: 67986

Other (OTH) AF: 0.584 AC: 1233 AN: 2112

Alfa AF: 0.584 Hom.: 13215

Bravo AF: 0.591

Asia WGS AF: 0.471 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.86
PhyloP100		3.3
Mutation Taster		=96/4	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: rs155102; hg19: chr2-182350447; COSMIC: COSV52004459;