chr2-181468234-A-G

Variant names:

• chr2-181468234-A-G
• rs3770132
• NM_000885.6:c.320-6726A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000885.6(ITGA4):​c.320-6726A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 152,228 control chromosomes in the GnomAD database, including 899 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 0.094 (899 hom., cov: 32)
• Consequence: ITGA4 NM_000885.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 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.320-6726A>G		intron	N/A	NP_000876.3	P13612-1
	ITGA4	NM_001316312.2		c.320-6726A>G		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.320-6726A>G		intron	N/A	ENSP00000380227.2	P13612-1
	ITGA4	ENST00000233573.6	TSL:1	c.320-6726A>G		intron	N/A	ENSP00000233573.6	E7EP60
	ITGA4	ENST00000339307.8	TSL:1	c.320-6726A>G		intron	N/A	ENSP00000340149.4	P13612-2

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14293 AN: 152110 Hom.: 898 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0939 AC: 14291 AN: 152228 Hom.: 899 Cov.: 32 AF XY: 0.0930 AC XY: 6920 AN XY: 74436

African (AFR) AF: 0.0261 AC: 1084 AN: 41550

American (AMR) AF: 0.0991 AC: 1515 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5170

South Asian (SAS) AF: 0.136 AC: 657 AN: 4828

European-Finnish (FIN) AF: 0.0722 AC: 766 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8452 AN: 67984

Other (OTH) AF: 0.113 AC: 239 AN: 2116

Alfa AF: 0.116 Hom.: 3536

Bravo AF: 0.0917

Asia WGS AF: 0.161 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.70
PhyloP100		-1.6
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: rs3770132; hg19: chr2-182332961;