NM_001394928.1:c.272G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394928.1(ITGA6):c.272G>A(p.Arg91Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R91P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ITGA6
NM_001394928.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.857

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059613496).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA6	NM_001394928.1	MANE Plus Clinical	c.272G>A	p.Arg91Gln	missense	Exon 2 of 26	NP_001381857.1	P23229-1
ITGA6	NM_000210.4	MANE Select	c.272G>A	p.Arg91Gln	missense	Exon 2 of 26	NP_000201.2	P23229-2
ITGA6	NM_001079818.3		c.272G>A	p.Arg91Gln	missense	Exon 2 of 25	NP_001073286.1	P23229-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.272G>A	p.Arg91Gln	missense	Exon 2 of 26	ENSP00000406694.1	P23229-1
ITGA6	ENST00000684293.1	MANE Select	c.272G>A	p.Arg91Gln	missense	Exon 2 of 26	ENSP00000508249.1	P23229-2
ITGA6	ENST00000264107.12	TSL:1	c.272G>A	p.Arg91Gln	missense	Exon 2 of 26	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251344

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.056

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.15

PhyloP100

0.86

PrimateAI

Benign

0.27

PROVEAN

Benign

0.31

REVEL

Benign

0.11

Sift

Benign

0.38

Sift4G

Benign

0.45

Polyphen

0.0010

Vest4

0.26

MVP

0.59

MPC

0.47

ClinPred

0.071

GERP RS

-1.4

Varity_R

0.062

gMVP

0.28

Mutation Taster

=94/6

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over