rs1043390

Positions:

Variant summary

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

The NM_004517.4(ILK):c.819G>A(p.Pro273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,613,698 control chromosomes in the GnomAD database, including 59,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P273P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.32 ( 8677 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51190 hom. )

Consequence

ILK
NM_004517.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0440

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=-0.56).

BP6

Variant 11-6609602-G-A is Benign according to our data. Variant chr11-6609602-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6609602-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.044 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ILK	NM_004517.4 linkuse as main transcript	c.819G>A	p.Pro273=	synonymous_variant	9/13	ENST00000299421.9
TAF10	NM_006284.4 linkuse as main transcript	c.*1320C>T		3_prime_UTR_variant	5/5	ENST00000299424.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ILK	ENST00000299421.9 linkuse as main transcript	c.819G>A	p.Pro273=	synonymous_variant	9/13	1	NM_004517.4	P1	Q13418-1
TAF10	ENST00000299424.9 linkuse as main transcript	c.*1320C>T		3_prime_UTR_variant	5/5	1	NM_006284.4	P1
	ENST00000527398.1 linkuse as main transcript	n.228+306C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48861

AN:

151920

Hom.:

8642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.271

AC:

68030

AN:

251450

Hom.:

9751

AF XY:

0.267

AC XY:

36242

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.342

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.261

AC:

381447

AN:

1461660

Hom.:

51190

Cov.:

AF XY:

0.259

AC XY:

188654

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.483

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.255

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.322

AC:

48951

AN:

152038

Hom.:

8677

Cov.:

AF XY:

0.318

AC XY:

23659

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.270

Hom.:

4138

Bravo

AF:

0.330

Asia WGS

AF:

0.286

AC:

997

AN:

3478

EpiCase

AF:

0.255

EpiControl

AF:

0.256

ClinVar

Significance: Benign/Likely 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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Pro273Pro in exon 9 of ILK: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 47.4% (2088/4402) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs1043390). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2014	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. -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	May 17, 2022	This alteration is classified as likely 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. -

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

-0.56

CADD

Benign

DANN

Benign

0.85

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