rs1574028

Variant names:

• chr2-172469112-C-A
• rs1574028
• NM_001394928.1:c.388-13C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394928.1(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_001394928.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0790
• Publications: 14 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-AS1 (HGNC:40308): (ITGA6 antisense RNA 1)

PDK1-AS1 (HGNC:40441): (PDK1 and ITGA6 antisense RNA 1)

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.388-13C>A		intron_variant	Intron 3 of 25	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.388-13C>A		intron_variant	Intron 3 of 25	ENST00000684293.1	NP_000201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.388-13C>A		intron_variant	Intron 3 of 25	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.388-13C>A		intron_variant	Intron 3 of 25		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9720 AN: 152102 Hom.: 426 Cov.: 32

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

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.: 32 AF XY: 0.0855 AC XY: 62143 AN XY: 726964

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

GnomAD4 genome AF: 0.0639 AC: 9723 AN: 152218 Hom.: 425 Cov.: 32 AF XY: 0.0630 AC XY: 4686 AN XY: 74424

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: 94 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: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0854 AC: 5808 AN: 67996

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0839 Hom.: 576

Bravo AF: 0.0672

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Junctional epidermolysis bullosa with pyloric atresia Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.9
DANN	Benign	0.73
PhyloP100		-0.079
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1574028; hg19: chr2-173333840;