rs17664

Variant names:

• chr2-172504503-A-G
• rs17664
• NM_001394928.1:c.*251A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-172504503-A-G
• chr2-172504503-A-T

Variant summary

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

The NM_000210.4(ITGA6):​c.*435A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 328,542 control chromosomes in the GnomAD database, including 42,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (21041 hom., cov: 33)
  • Exomes 𝑓: 0.47 (21462 hom.)
• Consequence: ITGA6 NM_000210.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.165
• Publications: 24 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=-0.73).
• BP6: Variant 2-172504503-A-G is Benign according to our data. Variant chr2-172504503-A-G is described in ClinVar as Benign. ClinVar VariationId is 332395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	NM_001394928.1	MANE Plus Clinical	c.*251A>G		3_prime_UTR	Exon 26 of 26	NP_001381857.1	P23229-1
	ITGA6	NM_000210.4	MANE Select	c.*435A>G		3_prime_UTR	Exon 26 of 26	NP_000201.2	P23229-2
	ITGA6	NM_001079818.3		c.*251A>G		3_prime_UTR	Exon 25 of 25	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.*251A>G		3_prime_UTR	Exon 26 of 26	ENSP00000406694.1	P23229-1
	ITGA6	ENST00000684293.1	MANE Select	c.*435A>G		3_prime_UTR	Exon 26 of 26	ENSP00000508249.1	P23229-2
	ITGA6	ENST00000264107.12	TSL:1	c.*435A>G		3_prime_UTR	Exon 26 of 26	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77449 AN: 151942 Hom.: 21006 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.472 AC: 83282 AN: 176482 Hom.: 21462 Cov.: 3 AF XY: 0.478 AC XY: 44366 AN XY: 92778

African (AFR) AF: 0.661 AC: 3393 AN: 5132

American (AMR) AF: 0.571 AC: 3710 AN: 6496

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 2334 AN: 5896

East Asian (EAS) AF: 0.876 AC: 9819 AN: 11214

South Asian (SAS) AF: 0.623 AC: 11270 AN: 18096

European-Finnish (FIN) AF: 0.489 AC: 4594 AN: 9402

Middle Eastern (MID) AF: 0.454 AC: 353 AN: 778

European-Non Finnish (NFE) AF: 0.394 AC: 42839 AN: 108742

Other (OTH) AF: 0.463 AC: 4970 AN: 10726

GnomAD4 genome AF: 0.510 AC: 77548 AN: 152060 Hom.: 21041 Cov.: 33 AF XY: 0.519 AC XY: 38601 AN XY: 74332

African (AFR) AF: 0.654 AC: 27110 AN: 41482

American (AMR) AF: 0.529 AC: 8073 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3468

East Asian (EAS) AF: 0.872 AC: 4511 AN: 5172

South Asian (SAS) AF: 0.631 AC: 3038 AN: 4818

European-Finnish (FIN) AF: 0.508 AC: 5365 AN: 10570

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26528 AN: 67964

Other (OTH) AF: 0.489 AC: 1031 AN: 2110

Alfa AF: 0.432 Hom.: 41021

Bravo AF: 0.520

Asia WGS AF: 0.739 AC: 2567 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Junctional epidermolysis bullosa with pyloric atresia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs17664; hg19: chr2-173369231;