11-6603786-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_004517.4(ILK):​c.-129G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 368,476 control chromosomes in the GnomAD database, including 2,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (758 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1500 hom.)
• Consequence: ILK NM_004517.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.46

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 11-6603786-G-T is Benign according to our data. Variant chr11-6603786-G-T is described in ClinVar as [Benign]. Clinvar id is 671499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILK	NM_004517.4	c.-129G>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000299421.9	NP_004508.1
RRP8	NM_015324.4	c.-284C>A		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>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_004517.4	ENSP00000299421.4
RRP8	ENST00000254605.11	c.-284C>A		upstream_gene_variant		1	NM_015324.4	ENSP00000254605.6

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13237 AN: 152102 Hom.: 758 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.108 AC: 23298 AN: 216266 Hom.: 1500 Cov.: 0 AF XY: 0.110 AC XY: 12266 AN XY: 111622

African (AFR) AF: 0.0200 AC: 98 AN: 4912

American (AMR) AF: 0.0748 AC: 390 AN: 5216

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 805 AN: 7148

East Asian (EAS) AF: 0.000680 AC: 10 AN: 14700

South Asian (SAS) AF: 0.171 AC: 2495 AN: 14592

European-Finnish (FIN) AF: 0.121 AC: 1921 AN: 15888

Middle Eastern (MID) AF: 0.0826 AC: 93 AN: 1126

European-Non Finnish (NFE) AF: 0.116 AC: 16057 AN: 139018

Other (OTH) AF: 0.105 AC: 1429 AN: 13666

GnomAD4 genome AF: 0.0870 AC: 13240 AN: 152210 Hom.: 758 Cov.: 32 AF XY: 0.0885 AC XY: 6584 AN XY: 74408

African (AFR) AF: 0.0217 AC: 902 AN: 41554

American (AMR) AF: 0.0865 AC: 1324 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5170

South Asian (SAS) AF: 0.160 AC: 774 AN: 4826

European-Finnish (FIN) AF: 0.135 AC: 1426 AN: 10598

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8148 AN: 67970

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0955 Hom.: 585

Bravo AF: 0.0770

Asia WGS AF: 0.0740 AC: 259 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

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	-0.30
CADD	Benign	22
DANN	Benign	0.94
PhyloP100		1.5
PromoterAI		-0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Publications

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Other links and lift over

dbSNP: rs11607058; hg19: chr11-6625016;