Genetic Variant ENST00000715295.1:c.-369-15408A>G (chr2-172352363-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.-369-15408A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,086 control chromosomes in the GnomAD database, including 52,136 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 0.82 ( 52136 hom., cov: 31)

Consequence

ITGA6
ENST00000715295.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.960

Publications

3 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=-0.86).

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.2666-15408A>G	intron_variant	Intron 4 of 5
LOC107985960	XR_001739775.3 link	n.2522-15408A>G	intron_variant	Intron 3 of 4
LOC107985960	XR_001739776.2 link	n.431-15408A>G	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ITGA6	ENST00000715295.1 link	c.-369-15408A>G	intron_variant	Intron 2 of 27	ENSP00000520448.1
ENSG00000232555	ENST00000657632.1 link	n.239-15408A>G	intron_variant	Intron 2 of 2
ENSG00000232555	ENST00000671082.1 link	n.862-15408A>G	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124252

AN:

151968

Hom.:

52108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.767

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.810

Gnomad ASJ

AF:

0.869

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.814

Gnomad MID

AF:

0.895

Gnomad NFE

AF:

0.902

Gnomad OTH

AF:

0.828

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

GnomAD4 genome

AF:

0.818

AC:

124337

AN:

152086

Hom.:

52136

Cov.:

AF XY:

0.807

AC XY:

59986

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.767

AC:

31828

AN:

41484

American (AMR)

AF:

0.810

AC:

12369

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.869

AC:

3015

AN:

3470

East Asian (EAS)

AF:

0.240

AC:

1232

AN:

5136

South Asian (SAS)

AF:

0.640

AC:

3074

AN:

4806

European-Finnish (FIN)

AF:

0.814

AC:

8628

AN:

10594

Middle Eastern (MID)

AF:

0.897

AC:

262

AN:

292

European-Non Finnish (NFE)

AF:

0.902

AC:

61367

AN:

68000

Other (OTH)

AF:

0.823

AC:

1742

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1028

2056

3083

4111

5139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.872

Hom.:

71050

Bravo

AF:

0.810

Asia WGS

AF:

0.484

AC:

1689

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.2

(source)

DANN

Benign

0.43

PhyloP100

0.96

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