chr11-6603786-G-A

Variant names:

• chr11-6603786-G-A
• rs11607058
• NM_004517.4:c.-129G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004517.4(ILK):​c.-129G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000462 in 216,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: ILK NM_004517.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• 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]

ENSG00000254400 (HGNC:):

RRP8 (HGNC:29030): (ribosomal RNA processing 8) Enables methylated histone binding activity. Involved in several processes, including cellular response to glucose starvation; intrinsic apoptotic signaling pathway by p53 class mediator; and regulation of gene expression. Located in several cellular components, including cytosol; nuclear lumen; and rDNA heterochromatin. Part of chromatin silencing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILK	NM_004517.4	c.-129G>A		5_prime_UTR_variant	Exon 1 of 13	ENST00000299421.9	NP_004508.1
RRP8	NM_015324.4	c.-284C>T		upstream_gene_variant		ENST00000254605.11	NP_056139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILK	ENST00000299421.9	c.-129G>A		5_prime_UTR_variant	Exon 1 of 13	1	NM_004517.4	ENSP00000299421.4
RRP8	ENST00000254605.11	c.-284C>T		upstream_gene_variant		1	NM_015324.4	ENSP00000254605.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000462 AC: 1 AN: 216504 Hom.: 0 Cov.: 0 AF XY: 0.00000895 AC XY: 1 AN XY: 111736

African (AFR) AF: 0.00 AC: 0 AN: 4916

American (AMR) AF: 0.00 AC: 0 AN: 5220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7152

East Asian (EAS) AF: 0.00 AC: 0 AN: 14700

South Asian (SAS) AF: 0.0000685 AC: 1 AN: 14602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 139204

Other (OTH) AF: 0.00 AC: 0 AN: 13672

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.97
PhyloP100		1.5
PromoterAI		0.43	Neutral

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: rs11607058; hg19: chr11-6625016;