Genetic Variant ITGA6:c.183-302T>A (chr2-172465237-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000210.4(ITGA6):c.183-302T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 451,198 control chromosomes in the GnomAD database, including 36,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12260 hom., cov: 32)

Exomes 𝑓: 0.38 ( 24299 hom. )

Consequence

ITGA6
NM_000210.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.550

Variant links:

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 links:

ITGA6-AS1 (HGNC:40308): (ITGA6 antisense RNA 1)

ITGA6-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-172465237-T-A is Benign according to our data. Variant chr2-172465237-T-A is described in ClinVar as [Benign]. Clinvar id is 1267500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1 link	c.183-302T>A		intron_variant	Intron 1 of 25	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4 link	c.183-302T>A		intron_variant	Intron 1 of 25	ENST00000684293.1	NP_000201.2	P23229-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6 link	c.183-302T>A		intron_variant	Intron 1 of 25	5	NM_001394928.1	ENSP00000406694.1		P23229-1
ITGA6	ENST00000684293.1 link	c.183-302T>A		intron_variant	Intron 1 of 25		NM_000210.4	ENSP00000508249.1		P23229-2

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58743

AN:

151846

Hom.:

12223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.426

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.364

GnomAD4 exome

AF:

0.378

AC:

113027

AN:

299234

Hom.:

24299

Cov.:

AF XY:

0.387

AC XY:

61573

AN XY:

159088

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.296

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.387

AC:

58842

AN:

151964

Hom.:

12260

Cov.:

AF XY:

0.398

AC XY:

29564

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.437

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.805

Gnomad4 SAS

AF:

0.518

Gnomad4 FIN

AF:

0.426

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.344

Hom.:

1234

Bravo

AF:

0.393

Asia WGS

AF:

0.633

AC:

2196

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.59

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over