11-6609311-C-T

Position:

chr11-6609311-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004517.4(ILK):c.631C>T(p.Arg211Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00117 in 1,614,040 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

ILK
NM_004517.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: 5.36

Variant links:

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 links:

TAF10 (HGNC:11543): (TATA-box binding protein associated factor 10) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the small subunits of TFIID that is associated with a subset of TFIID complexes. Studies with human and mammalian cells have shown that this subunit is required for transcriptional activation by the estrogen receptor, for progression through the cell cycle, and may also be required for certain cellular differentiation programs. [provided by RefSeq, Jul 2008]

TAF10 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025575578).

BP6

Variant 11-6609311-C-T is Benign according to our data. Variant chr11-6609311-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 155799.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr11-6609311-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 182 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILK	NM_004517.4 linkuse as main transcript	c.631C>T	p.Arg211Cys	missense_variant	8/13	ENST00000299421.9	NP_004508.1
TAF10	NM_006284.4 linkuse as main transcript	c.*1611G>A		3_prime_UTR_variant	5/5	ENST00000299424.9	NP_006275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILK	ENST00000299421.9 linkuse as main transcript	c.631C>T	p.Arg211Cys	missense_variant	8/13	1	NM_004517.4	ENSP00000299421	P1	Q13418-1
TAF10	ENST00000299424.9 linkuse as main transcript	c.*1611G>A		3_prime_UTR_variant	5/5	1	NM_006284.4	ENSP00000299424	P1
	ENST00000527398.1 linkuse as main transcript	n.229-333G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000955

AC:

240

AN:

251402

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00117

AC:

1710

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

819

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00120

AC:

182

AN:

152272

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00141

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000840

AC:

102

EpiCase

AF:

0.00196

EpiControl

AF:

0.00124

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2017	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. -
Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 12, 2019	The ILK c.631C>T; p.Arg211Cys variant (rs140322345) is reported in the literature in a cohort of individuals with dilated cardiomyopathy (Haas 2015). This variant is found in the Latino population with an overall allele frequency of 0.21% (74/35440 alleles) in the Genome Aggregation Database. The arginine at codon 211 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Arg211Cys variant is uncertain at this time. References: Haas J et al. Atlas of the clinical genetics of human dilated cardiomyopathy. Eur Heart J. 2015 May 7;36(18):1123-35a. -

Primary familial hypertrophic cardiomyopathy

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Blueprint Genetics	Dec 20, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

ILK-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.69

.;D;T;D;.;D

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;.;D;.;D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.026

T;T;T;T;T;T

MetaSVM

Uncertain

0.56

MutationAssessor

Uncertain

2.9

.;M;.;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.5

.;D;.;D;D;D

REVEL

Pathogenic

0.82

Sift

Uncertain

0.0040

.;D;.;D;D;D

Sift4G

Uncertain

0.058

T;D;D;D;D;D

Polyphen

0.86

.;P;.;P;.;P

Vest4

0.64

MVP

0.97

MPC

1.1

ClinPred

0.060

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over