rs1043390

Variant names:

• chr11-6609602-G-A
• rs1043390
• NM_004517.4:c.819G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-6609602-G-A
• chr11-6609602-G-C
• chr11-6609602-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004517.4(ILK):​c.819G>A​(p.Pro273Pro) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0440
• Publications: 22 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]

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]

ENSG00000254641 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 137590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004517.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILK	NM_004517.4	MANE Select	c.819G>A	p.Pro273Pro	synonymous	Exon 9 of 13	NP_004508.1	Q13418-1
	TAF10	NM_006284.4	MANE Select	c.*1320C>T		3_prime_UTR	Exon 5 of 5	NP_006275.1	Q12962
	ILK	NM_001014794.3		c.819G>A	p.Pro273Pro	synonymous	Exon 9 of 13	NP_001014794.1	Q13418-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILK	ENST00000299421.9	TSL:1 MANE Select	c.819G>A	p.Pro273Pro	synonymous	Exon 9 of 13	ENSP00000299421.4	Q13418-1
	ILK	ENST00000396751.6	TSL:1	c.819G>A	p.Pro273Pro	synonymous	Exon 8 of 12	ENSP00000379975.2	Q13418-1
	ILK	ENST00000420936.6	TSL:1	c.819G>A	p.Pro273Pro	synonymous	Exon 9 of 13	ENSP00000403487.2	Q13418-1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48861 AN: 151920 Hom.: 8642 Cov.: 32

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

GnomAD2 exomes AF: 0.271 AC: 68030 AN: 251450 AF XY: 0.267

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 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.: 41 AF XY: 0.259 AC XY: 188654 AN XY: 727150

African (AFR) AF: 0.483 AC: 16176 AN: 33476

American (AMR) AF: 0.215 AC: 9635 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7533 AN: 26136

East Asian (EAS) AF: 0.331 AC: 13155 AN: 39698

South Asian (SAS) AF: 0.237 AC: 20430 AN: 86256

European-Finnish (FIN) AF: 0.244 AC: 13048 AN: 53406

Middle Eastern (MID) AF: 0.296 AC: 1705 AN: 5768

European-Non Finnish (NFE) AF: 0.255 AC: 283230 AN: 1111802

Other (OTH) AF: 0.274 AC: 16535 AN: 60394

GnomAD4 genome AF: 0.322 AC: 48951 AN: 152038 Hom.: 8677 Cov.: 32 AF XY: 0.318 AC XY: 23659 AN XY: 74318

African (AFR) AF: 0.471 AC: 19523 AN: 41426

American (AMR) AF: 0.268 AC: 4097 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1782 AN: 5164

South Asian (SAS) AF: 0.244 AC: 1172 AN: 4812

European-Finnish (FIN) AF: 0.243 AC: 2575 AN: 10578

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17654 AN: 67982

Other (OTH) AF: 0.312 AC: 659 AN: 2114

Alfa AF: 0.273 Hom.: 4730

Bravo AF: 0.330

Asia WGS AF: 0.286 AC: 997 AN: 3478

EpiCase AF: 0.255

EpiControl AF: 0.256

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)
-	-	1	Primary familial hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		-0.044
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs1043390; hg19: chr11-6630833; COSMIC: COSV54990818; COSMIC: COSV54990818;