rs143318774

Variant names:

• chr11-6604141-A-G
• rs143318774
• ENST00000396751.6:c.-131A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-6604141-A-G
• chr11-6604141-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004517.4(ILK):​c.-92-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 829,908 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (6 hom.)
• Consequence: ILK NM_004517.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.123
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-6604141-A-G is Benign according to our data. Variant chr11-6604141-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 675791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 647 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILK	NM_004517.4	c.-92-39A>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.-92-39A>G		intron_variant	Intron 1 of 12	1	NM_004517.4	ENSP00000299421.4

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 643 AN: 152056 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.000502 AC: 340 AN: 677734 Hom.: 6 Cov.: 9 AF XY: 0.000404 AC XY: 144 AN XY: 356600

African (AFR) AF: 0.0154 AC: 278 AN: 18022

American (AMR) AF: 0.000466 AC: 16 AN: 34364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20350

East Asian (EAS) AF: 0.00 AC: 0 AN: 32408

South Asian (SAS) AF: 0.0000622 AC: 4 AN: 64342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33360

Middle Eastern (MID) AF: 0.000368 AC: 1 AN: 2714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 437730

Other (OTH) AF: 0.00119 AC: 41 AN: 34444

GnomAD4 genome AF: 0.00425 AC: 647 AN: 152174 Hom.: 5 Cov.: 32 AF XY: 0.00391 AC XY: 291 AN XY: 74390

African (AFR) AF: 0.0148 AC: 616 AN: 41508

American (AMR) AF: 0.00144 AC: 22 AN: 15306

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

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

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00448 Hom.: 0

Bravo AF: 0.00516

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.60
PhyloP100		0.12
PromoterAI		-0.0048	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143318774; hg19: chr11-6625371;