rs2555178

Variant names:

• chr11-6603972-G-C
• rs2555178
• ENST00000396751.6:c.-300G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004517.4(ILK):​c.-93+150G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00514 in 532,950 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (15 hom.)
• Consequence: ILK NM_004517.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0890
• Publications: 1 publications found

Genes affected

ILK (HGNC:6040): (integrin linked kinase) This gene encodes a protein with a kinase-like domain and four ankyrin-like repeats. The encoded protein associates at the cell membrane with the cytoplasmic domain of beta integrins, where it regulates integrin-mediated signal transduction. Activity of this protein is important in the epithelial to mesenchymal transition, and over-expression of this gene is implicated in tumor growth and metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ILK Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000254400 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-6603972-G-C is Benign according to our data. Variant chr11-6603972-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1318053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (2057/152112) while in subpopulation AFR AF = 0.0463 (1922/41470). AF 95% confidence interval is 0.0446. There are 43 homozygotes in GnomAd4. There are 959 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2057 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILK	NM_004517.4	c.-93+150G>C		intron_variant	Intron 1 of 12	ENST00000299421.9	NP_004508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILK	ENST00000299421.9	c.-93+150G>C		intron_variant	Intron 1 of 12	1	NM_004517.4	ENSP00000299421.4

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2050 AN: 151994 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00180 AC: 684 AN: 380838 Hom.: 15 Cov.: 0 AF XY: 0.00146 AC XY: 292 AN XY: 200240

African (AFR) AF: 0.0444 AC: 491 AN: 11058

American (AMR) AF: 0.00392 AC: 64 AN: 16312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11864

East Asian (EAS) AF: 0.00 AC: 0 AN: 25106

South Asian (SAS) AF: 0.0000697 AC: 3 AN: 43018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23168

Middle Eastern (MID) AF: 0.00179 AC: 3 AN: 1678

European-Non Finnish (NFE) AF: 0.000159 AC: 36 AN: 226480

Other (OTH) AF: 0.00393 AC: 87 AN: 22154

GnomAD4 genome AF: 0.0135 AC: 2057 AN: 152112 Hom.: 43 Cov.: 32 AF XY: 0.0129 AC XY: 959 AN XY: 74354

African (AFR) AF: 0.0463 AC: 1922 AN: 41470

American (AMR) AF: 0.00634 AC: 97 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67998

Other (OTH) AF: 0.0123 AC: 26 AN: 2106

Alfa AF: 0.00950 Hom.: 2

Bravo AF: 0.0155

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 11, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.50
PhyloP100		-0.089
PromoterAI		0.072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2555178; hg19: chr11-6625202;