NM_001394928.1:c.182+16920C>A

Variant names:

• chr2-172444890-C-A
• rs13410475
• NM_001394928.1:c.182+16920C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394928.1(ITGA6):​c.182+16920C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 152,096 control chromosomes in the GnomAD database, including 453 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 0.067 (453 hom., cov: 28)
• Consequence: ITGA6 NM_001394928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885
• Publications: 11 publications found

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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• epidermolysis bullosa, junctional 6, with pyloric atresia

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	NM_001394928.1	MANE Plus Clinical	c.182+16920C>A		intron	N/A	NP_001381857.1	P23229-1
	ITGA6	NM_000210.4	MANE Select	c.182+16920C>A		intron	N/A	NP_000201.2	P23229-2
	ITGA6	NM_001079818.3		c.182+16920C>A		intron	N/A	NP_001073286.1	P23229-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.182+16920C>A		intron	N/A	ENSP00000406694.1	P23229-1
	ITGA6	ENST00000684293.1	MANE Select	c.182+16920C>A		intron	N/A	ENSP00000508249.1	P23229-2
	ITGA6	ENST00000264107.12	TSL:1	c.182+16920C>A		intron	N/A	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10225 AN: 151978 Hom.: 453 Cov.: 28

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0583

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

GnomAD4 genome AF: 0.0673 AC: 10238 AN: 152096 Hom.: 453 Cov.: 28 AF XY: 0.0677 AC XY: 5036 AN XY: 74360

African (AFR) AF: 0.0644 AC: 2671 AN: 41486

American (AMR) AF: 0.0610 AC: 933 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0450 AC: 156 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1356 AN: 5160

South Asian (SAS) AF: 0.0894 AC: 430 AN: 4812

European-Finnish (FIN) AF: 0.0446 AC: 471 AN: 10570

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4013 AN: 67992

Other (OTH) AF: 0.0620 AC: 131 AN: 2114

Alfa AF: 0.0603 Hom.: 133

Bravo AF: 0.0701

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.81
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13410475; hg19: chr2-173309618;