rs12621278

Positions:

• chr2-172446825-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394928.1(ITGA6):​c.183-18714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 152,266 control chromosomes in the GnomAD database, including 366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.052 (366 hom., cov: 32)
• Consequence: ITGA6 NM_001394928.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.286

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-172446825-A-G is Benign according to our data. Variant chr2-172446825-A-G is described in ClinVar as [Benign]. Clinvar id is 1599744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA6	NM_000210.4	c.183-18714A>G		intron_variant		ENST00000684293.1	NP_000201.2
ITGA6	NM_001394928.1	c.183-18714A>G		intron_variant		ENST00000442250.6	NP_001381857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.183-18714A>G		intron_variant		5	NM_001394928.1	ENSP00000406694
ITGA6	ENST00000684293.1	c.183-18714A>G		intron_variant			NM_000210.4	ENSP00000508249	P3

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7967 AN: 152148 Hom.: 366 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0499

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

GnomAD4 genome AF: 0.0524 AC: 7976 AN: 152266 Hom.: 366 Cov.: 32 AF XY: 0.0533 AC XY: 3972 AN XY: 74454

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0589

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0643 Hom.: 714

Bravo AF: 0.0532

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs12621278; hg19: chr2-173311553; COSMIC: COSV51219654;