rs2292195

Positions:

chr11-6609785-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004517.4(ILK):c.918C>T(p.Ala306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,613,950 control chromosomes in the GnomAD database, including 50,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3906 hom., cov: 33)

Exomes 𝑓: 0.25 ( 46454 hom. )

Consequence

ILK
NM_004517.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.550

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-6609785-C-T is Benign according to our data. Variant chr11-6609785-C-T is described in ClinVar as [Benign]. Clinvar id is 137591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6609785-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILK	NM_004517.4 linkuse as main transcript	c.918C>T	p.Ala306=	synonymous_variant	10/13	ENST00000299421.9	NP_004508.1
TAF10	NM_006284.4 linkuse as main transcript	c.*1137G>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.918C>T	p.Ala306=	synonymous_variant	10/13	1	NM_004517.4	ENSP00000299421	P1	Q13418-1
TAF10	ENST00000299424.9 linkuse as main transcript	c.*1137G>A		3_prime_UTR_variant	5/5	1	NM_006284.4	ENSP00000299424	P1
	ENST00000527398.1 linkuse as main transcript	n.228+123G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33089

AN:

151968

Hom.:

3903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.228

AC:

57404

AN:

251478

Hom.:

6979

AF XY:

0.226

AC XY:

30699

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.249

AC:

363420

AN:

1461864

Hom.:

46454

Cov.:

AF XY:

0.247

AC XY:

179468

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.248

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.230

GnomAD4 genome

AF:

0.218

AC:

33100

AN:

152086

Hom.:

3906

Cov.:

AF XY:

0.216

AC XY:

16094

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.244

Hom.:

2719

Bravo

AF:

0.210

Asia WGS

AF:

0.148

AC:

516

AN:

3478

EpiCase

AF:

0.257

EpiControl

AF:

0.254

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Feb 07, 2019	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 22, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ala306Ala in exon 10 of ILK: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 26.5% (2274/8592) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2292195). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Primary familial hypertrophic cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.88

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

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