2-172470098-G-T

Variant names:

• chr2-172470098-G-T
• rs6743724
• NM_001394928.1:c.643+718G>T

Variant summary

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

The NM_001394928.1(ITGA6):​c.643+718G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,990 control chromosomes in the GnomAD database, including 16,530 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 0.44 (16530 hom., cov: 32)
• Consequence: ITGA6 NM_001394928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 7 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-AS1 (HGNC:40308): (ITGA6 antisense RNA 1)

PDK1-AS1 (HGNC:40441): (PDK1 and ITGA6 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.643+718G>T		intron_variant	Intron 4 of 25	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.643+718G>T		intron_variant	Intron 4 of 25	ENST00000684293.1	NP_000201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.643+718G>T		intron_variant	Intron 4 of 25	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.643+718G>T		intron_variant	Intron 4 of 25		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66990 AN: 151872 Hom.: 16479 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.442 AC: 67109 AN: 151990 Hom.: 16530 Cov.: 32 AF XY: 0.452 AC XY: 33598 AN XY: 74322

African (AFR) AF: 0.611 AC: 25330 AN: 41450

American (AMR) AF: 0.469 AC: 7158 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1181 AN: 3472

East Asian (EAS) AF: 0.834 AC: 4320 AN: 5180

South Asian (SAS) AF: 0.605 AC: 2918 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4449 AN: 10542

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20459 AN: 67942

Other (OTH) AF: 0.415 AC: 873 AN: 2102

Alfa AF: 0.350 Hom.: 3536

Bravo AF: 0.453

Asia WGS AF: 0.700 AC: 2430 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.31
DANN	Benign	0.62
PhyloP100		-0.64
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: rs6743724; hg19: chr2-173334826;