Genetic Variant NM_001394928.1:c.*251A>T (chr2-172504503-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394928.1(ITGA6):c.*251A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 329,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ITGA6
NM_001394928.1 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165

Publications

24 publications found

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:

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

PDK1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394928.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGA6	NM_001394928.1	MANE Plus Clinical	c.*251A>T	3_prime_UTR	Exon 26 of 26	NP_001381857.1	P23229-1
ITGA6	NM_000210.4	MANE Select	c.*435A>T	3_prime_UTR	Exon 26 of 26	NP_000201.2	P23229-2
ITGA6	NM_001079818.3		c.*251A>T	3_prime_UTR	Exon 25 of 25	NP_001073286.1	P23229-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.*251A>T	3_prime_UTR	Exon 26 of 26	ENSP00000406694.1	P23229-1
ITGA6	ENST00000684293.1	MANE Select	c.*435A>T	3_prime_UTR	Exon 26 of 26	ENSP00000508249.1	P23229-2
ITGA6	ENST00000264107.12	TSL:1	c.*435A>T	3_prime_UTR	Exon 26 of 26	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000113

AC:

AN:

177224

Hom.:

Cov.:

AF XY:

0.0000107

AC XY:

AN XY:

93154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5142

American (AMR)

AF:

0.00

AC:

AN:

6520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5922

East Asian (EAS)

AF:

0.00

AC:

AN:

11234

South Asian (SAS)

AF:

0.00

AC:

AN:

18162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

780

European-Non Finnish (NFE)

AF:

0.00000916

AC:

AN:

109222

Other (OTH)

AF:

0.0000927

AC:

AN:

10790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

41021

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Junctional epidermolysis bullosa with pyloric atresia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.17

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over