Genetic Variant ITGA6:c.388-13C>A (chr2-172469112-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000210.4(ITGA6):c.388-13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 1,613,436 control chromosomes in the GnomAD database, including 6,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 425 hom., cov: 32)

Exomes 𝑓: 0.087 ( 5936 hom. )

Consequence

ITGA6
NM_000210.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0790

Publications

14 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-172469112-C-A is Benign according to our data. Variant chr2-172469112-C-A is described in ClinVar as Benign. ClinVar VariationId is 332358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000210.4. 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.388-13C>A	intron	N/A	NP_001381857.1	P23229-1
ITGA6	NM_000210.4	MANE Select	c.388-13C>A	intron	N/A	NP_000201.2	P23229-2
ITGA6	NM_001079818.3		c.388-13C>A	intron	N/A	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.388-13C>A	intron	N/A	ENSP00000406694.1	P23229-1
ITGA6	ENST00000684293.1	MANE Select	c.388-13C>A	intron	N/A	ENSP00000508249.1	P23229-2
ITGA6	ENST00000264107.12	TSL:1	c.388-13C>A	intron	N/A	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes

AF:

0.0639

AC:

9720

AN:

152102

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.0578

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0854

Gnomad OTH

AF:

0.0656

GnomAD2 exomes

AF:

0.0786

AC:

19767

AN:

251334

AF XY:

0.0768

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.0578

Gnomad NFE exome

AF:

0.0856

Gnomad OTH exome

AF:

0.0746

GnomAD4 exome

AF:

0.0866

AC:

126614

AN:

1461218

Hom.:

5936

Cov.:

AF XY:

0.0855

AC XY:

62143

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.0142

AC:

477

AN:

33478

American (AMR)

AF:

0.139

AC:

6236

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

2728

AN:

26124

East Asian (EAS)

AF:

0.0161

AC:

639

AN:

39698

South Asian (SAS)

AF:

0.0588

AC:

5069

AN:

86214

European-Finnish (FIN)

AF:

0.0584

AC:

3117

AN:

53414

Middle Eastern (MID)

AF:

0.0761

AC:

439

AN:

5768

European-Non Finnish (NFE)

AF:

0.0926

AC:

102889

AN:

1111436

Other (OTH)

AF:

0.0832

AC:

5020

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

5328

10656

15983

21311

26639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3824

7648

11472

15296

19120

<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:

0.0639

AC:

9723

AN:

152218

Hom.:

425

Cov.:

AF XY:

0.0630

AC XY:

4686

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0188

AC:

781

AN:

41530

American (AMR)

AF:

0.105

AC:

1608

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

366

AN:

3472

East Asian (EAS)

AF:

0.0181

AC:

AN:

5188

South Asian (SAS)

AF:

0.0571

AC:

275

AN:

4820

European-Finnish (FIN)

AF:

0.0587

AC:

622

AN:

10602

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0854

AC:

5808

AN:

67996

Other (OTH)

AF:

0.0644

AC:

136

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

458

917

1375

1834

2292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0839

Hom.:

576

Bravo

AF:

0.0672

Asia WGS

AF:

0.0400

AC:

141

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Junctional epidermolysis bullosa with pyloric atresia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.9

(source)

DANN

Benign

0.73

PhyloP100

-0.079

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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