ENST00000715295.1:c.-536+27505A>G

Variant names:

• chr2-172261762-A-G
• rs4289149
• ENST00000715295.1:c.-536+27505A>G

Variant summary

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

The ENST00000715295.1(ITGA6):​c.-536+27505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,070 control chromosomes in the GnomAD database, including 47,082 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 0.78 (47082 hom., cov: 31)
• Consequence: ITGA6 ENST00000715295.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650
• Publications: 3 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]

DLX2-DT (HGNC:50638): (DLX2 divergent transcript)

LOC107985960 (HGNC:):

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 = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107985960	XR_001739773.3	n.2208+9129A>G		intron_variant	Intron 1 of 5
LOC107985960	XR_001739775.3	n.2208+9129A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000715295.1	c.-536+27505A>G		intron_variant	Intron 1 of 27			ENSP00000520448.1
DLX2-DT	ENST00000662340.1	n.213-36435A>G		intron_variant	Intron 2 of 3
DLX2-DT	ENST00000667725.1	n.242-36435A>G		intron_variant	Intron 2 of 4
DLX2-DT	ENST00000715288.1	n.457-36441A>G		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119159 AN: 151952 Hom.: 47076 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.784 AC: 119197 AN: 152070 Hom.: 47082 Cov.: 31 AF XY: 0.788 AC XY: 58579 AN XY: 74318

African (AFR) AF: 0.679 AC: 28148 AN: 41460

American (AMR) AF: 0.821 AC: 12544 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2896 AN: 3470

East Asian (EAS) AF: 0.950 AC: 4917 AN: 5174

South Asian (SAS) AF: 0.782 AC: 3758 AN: 4808

European-Finnish (FIN) AF: 0.829 AC: 8760 AN: 10572

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55514 AN: 67994

Other (OTH) AF: 0.788 AC: 1662 AN: 2110

Alfa AF: 0.807 Hom.: 199051

Bravo AF: 0.779

Asia WGS AF: 0.806 AC: 2804 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	4.2
DANN	Benign	0.81
PhyloP100		0.65

Splicing

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

Other links and lift over

dbSNP: rs4289149; hg19: chr2-173126490;