11-6603972-G-C

Position:

• chr11-6603972-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000396751.6(ILK):​c.-300G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00514 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 ENST00000396751.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0890

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2057 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ILK	NM_004517.4	c.-93+150G>C		intron_variant		ENST00000299421.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILK	ENST00000299421.9	c.-93+150G>C		intron_variant		1	NM_004517.4	P1
	ENST00000527191.1	n.362+87C>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.0444

Gnomad4 AMR exome AF: 0.00392

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000697

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.00393

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

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0123

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs2555178; hg19: chr11-6625202;