rs2141698

Variant names:

• chr2-172425667-T-C
• rs2141698
• ENST00000715295.1:c.-160-39872T>C

Variant summary

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

The ENST00000715295.1(ITGA6):​c.-160-39872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,158 control chromosomes in the GnomAD database, including 52,027 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 0.83 (52027 hom., cov: 32)
• Consequence: ITGA6 ENST00000715295.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• Publications: 16 publications found

Genes affected

ITGA6 (HGNC:6142): (integrin subunit alpha 6) 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 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ITGA6 Gene-Disease associations (from GenCC):

• junctional epidermolysis bullosa with pyloric atresia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• epidermolysis bullosa, junctional 6, with pyloric atresia

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000715295.1	c.-160-39872T>C		intron_variant	Intron 4 of 27			ENSP00000520448.1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125591 AN: 152040 Hom.: 51987 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.826 AC: 125684 AN: 152158 Hom.: 52027 Cov.: 32 AF XY: 0.826 AC XY: 61418 AN XY: 74398

African (AFR) AF: 0.827 AC: 34291 AN: 41478

American (AMR) AF: 0.854 AC: 13063 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2441 AN: 3468

East Asian (EAS) AF: 0.909 AC: 4706 AN: 5176

South Asian (SAS) AF: 0.672 AC: 3242 AN: 4822

European-Finnish (FIN) AF: 0.872 AC: 9244 AN: 10598

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56051 AN: 68002

Other (OTH) AF: 0.812 AC: 1719 AN: 2116

Alfa AF: 0.818 Hom.: 112893

Bravo AF: 0.830

Asia WGS AF: 0.808 AC: 2813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.87
PhyloP100		-0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2141698; hg19: chr2-173290395;