rs1685903382

Variant names:

• chr2-181485906-C-G
• rs1685903382
• NM_000885.6:c.1067C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-181485906-C-G
• chr2-181485906-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000885.6(ITGA4):​c.1067C>G​(p.Thr356Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGA4 NM_000885.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.884
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08726984).

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.1067C>G	p.Thr356Arg	missense	Exon 10 of 28	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.1067C>G	p.Thr356Arg	missense	Exon 10 of 28	ENSP00000380227.2	P13612-1
	ITGA4	ENST00000233573.6	TSL:1	c.1067C>G	p.Thr356Arg	missense	Exon 10 of 16	ENSP00000233573.6	E7EP60
	ITGA4	ENST00000465522.5	TSL:2	n.1318C>G		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.93	L
PhyloP100		0.88
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.058
Sift	Benign	0.63	T
Sift4G	Benign	0.37	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.49		Gain of methylation at T356 (P = 0.0435)
MVP		0.84
MPC		0.59
ClinPred		0.078	T
GERP RS		1.6
Varity_R		0.081
gMVP		0.84
Mutation Taster		=95/5	polymorphism

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: rs1685903382; hg19: chr2-182350633;