Genetic Variant ENST00000715295.1:c.-369-14610A>G (chr2-172353161-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000715295.1(ITGA6):c.-369-14610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,158 control chromosomes in the GnomAD database, including 54,258 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 0.83 ( 54258 hom., cov: 31)

Consequence

ITGA6
ENST00000715295.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.228

Publications

4 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 Gene-Disease associations (from GenCC):

junctional epidermolysis bullosa with pyloric atresia
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
epidermolysis bullosa, junctional 6, with pyloric atresia
Inheritance: AD Classification: LIMITED Submitted by: G2P

ITGA6 links:

ENSG00000232555 (HGNC:):

ENSG00000232555 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC107985960	XR_001739773.3 link	n.2666-14610A>G	intron_variant	Intron 4 of 5
LOC107985960	XR_001739775.3 link	n.2522-14610A>G	intron_variant	Intron 3 of 4
LOC107985960	XR_001739776.2 link	n.431-14610A>G	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ITGA6	ENST00000715295.1 link	c.-369-14610A>G	intron_variant	Intron 2 of 27	ENSP00000520448.1
ENSG00000232555	ENST00000657632.1 link	n.239-14610A>G	intron_variant	Intron 2 of 2
ENSG00000232555	ENST00000671082.1 link	n.862-14610A>G	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

126916

AN:

152038

Hom.:

54210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.816

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.814

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.902

Gnomad OTH

AF:

0.838

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

GnomAD4 genome

AF:

0.835

AC:

127024

AN:

152158

Hom.:

54258

Cov.:

AF XY:

0.824

AC XY:

61303

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.827

AC:

34320

AN:

41486

American (AMR)

AF:

0.816

AC:

12466

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.876

AC:

3039

AN:

3468

East Asian (EAS)

AF:

0.251

AC:

1299

AN:

5178

South Asian (SAS)

AF:

0.640

AC:

3082

AN:

4818

European-Finnish (FIN)

AF:

0.814

AC:

8617

AN:

10580

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.902

AC:

61358

AN:

68026

Other (OTH)

AF:

0.833

AC:

1760

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

941

1883

2824

3766

4707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.879

Hom.:

45658

Bravo

AF:

0.830

Asia WGS

AF:

0.492

AC:

1715

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.1

(source)

DANN

Benign

0.47

PhyloP100

-0.23

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over