11-6603807-T-C

Variant names:

• chr11-6603807-T-C
• rs139314477
• NM_004517.4:c.-108T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_004517.4(ILK):​c.-108T>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 0.000609 in 354,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: ILK NM_004517.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42
• 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]

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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 11-6603807-T-C is Benign according to our data. Variant chr11-6603807-T-C is described in ClinVar as [Benign]. Clinvar id is 137589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 177 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILK	NM_004517.4	c.-108T>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000299421.9	NP_004508.1
RRP8	NM_015324.4	c.-305A>G		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.-108T>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_004517.4	ENSP00000299421.4
RRP8	ENST00000254605.11	c.-305A>G		upstream_gene_variant		1	NM_015324.4	ENSP00000254605.6

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000193 AC: 39 AN: 202506 Hom.: 0 Cov.: 0 AF XY: 0.000190 AC XY: 20 AN XY: 105074

African (AFR) AF: 0.00439 AC: 20 AN: 4556

American (AMR) AF: 0.000367 AC: 2 AN: 5456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6506

East Asian (EAS) AF: 0.00 AC: 0 AN: 12710

South Asian (SAS) AF: 0.000309 AC: 5 AN: 16180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1028

European-Non Finnish (NFE) AF: 0.00000776 AC: 1 AN: 128890

Other (OTH) AF: 0.000860 AC: 11 AN: 12784

GnomAD4 genome AF: 0.00116 AC: 177 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74434

African (AFR) AF: 0.00407 AC: 169 AN: 41554

American (AMR) AF: 0.000261 AC: 4 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000971 Hom.: 0

Bravo AF: 0.00123

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 29, 2014

GeneDx

Significance: 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	-0.28
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		1.4
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs139314477; hg19: chr11-6625037;