ENST00000396751.6:c.-187A>G

Variant names:

• chr11-6604085-A-G
• rs2659861
• ENST00000396751.6:c.-187A>G

Variant summary

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

The ENST00000396751.6(ILK):​c.-187A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 647,970 control chromosomes in the GnomAD database, including 69 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 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (25 hom.)
• Consequence: ILK ENST00000396751.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.121
• Publications: 2 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=-0.83).
• BP6: Variant 11-6604085-A-G is Benign according to our data. Variant chr11-6604085-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0136 (2065/152078) while in subpopulation AFR AF = 0.0465 (1926/41456). AF 95% confidence interval is 0.0447. There are 44 homozygotes in GnomAd4. There are 966 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2065 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILK	NM_004517.4	c.-92-95A>G		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.-92-95A>G		intron_variant	Intron 1 of 12	1	NM_004517.4	ENSP00000299421.4

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2058 AN: 151960 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

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: 0.000147

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00188 AC: 931 AN: 495892 Hom.: 25 Cov.: 5 AF XY: 0.00149 AC XY: 392 AN XY: 263392

African (AFR) AF: 0.0458 AC: 666 AN: 14554

American (AMR) AF: 0.00334 AC: 99 AN: 29662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16008

East Asian (EAS) AF: 0.00 AC: 0 AN: 31404

South Asian (SAS) AF: 0.0000569 AC: 3 AN: 52746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30588

Middle Eastern (MID) AF: 0.00186 AC: 4 AN: 2152

European-Non Finnish (NFE) AF: 0.000151 AC: 44 AN: 290836

Other (OTH) AF: 0.00412 AC: 115 AN: 27942

GnomAD4 genome AF: 0.0136 AC: 2065 AN: 152078 Hom.: 44 Cov.: 32 AF XY: 0.0130 AC XY: 966 AN XY: 74326

African (AFR) AF: 0.0465 AC: 1926 AN: 41456

American (AMR) AF: 0.00667 AC: 102 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67986

Other (OTH) AF: 0.0123 AC: 26 AN: 2110

Alfa AF: 0.0106 Hom.: 3

Bravo AF: 0.0157

Asia WGS AF: 0.00289 AC: 10 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	-0.83
CADD	Benign	8.1
DANN	Benign	0.64
PhyloP100		-0.12
PromoterAI		0.017	Neutral
Mutation Taster		=300/0	polymorphism

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: rs2659861; hg19: chr11-6625315;