rs2292195

Variant names:

• chr11-6609785-C-T
• rs2292195
• NM_004517.4:c.918C>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.918C>T​(p.Ala306Ala) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.550
• Publications: 21 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=-0.53).
• BP6: Variant 11-6609785-C-T is Benign according to our data. Variant chr11-6609785-C-T is described in ClinVar as Benign. ClinVar VariationId is 137591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.918C>T	p.Ala306Ala	synonymous	Exon 10 of 13	NP_004508.1	Q13418-1
	TAF10	NM_006284.4	MANE Select	c.*1137G>A		3_prime_UTR	Exon 5 of 5	NP_006275.1	Q12962
	ILK	NM_001014794.3		c.918C>T	p.Ala306Ala	synonymous	Exon 10 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.918C>T	p.Ala306Ala	synonymous	Exon 10 of 13	ENSP00000299421.4	Q13418-1
	ILK	ENST00000396751.6	TSL:1	c.918C>T	p.Ala306Ala	synonymous	Exon 9 of 12	ENSP00000379975.2	Q13418-1
	ILK	ENST00000420936.6	TSL:1	c.918C>T	p.Ala306Ala	synonymous	Exon 10 of 13	ENSP00000403487.2	Q13418-1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33089 AN: 151968 Hom.: 3903 Cov.: 33

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

GnomAD2 exomes AF: 0.228 AC: 57404 AN: 251478 AF XY: 0.226

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 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.: 42 AF XY: 0.247 AC XY: 179468 AN XY: 727228

African (AFR) AF: 0.142 AC: 4747 AN: 33480

American (AMR) AF: 0.236 AC: 10561 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 6491 AN: 26134

East Asian (EAS) AF: 0.124 AC: 4915 AN: 39700

South Asian (SAS) AF: 0.163 AC: 14045 AN: 86256

European-Finnish (FIN) AF: 0.292 AC: 15595 AN: 53416

Middle Eastern (MID) AF: 0.212 AC: 1220 AN: 5764

European-Non Finnish (NFE) AF: 0.263 AC: 291935 AN: 1111994

Other (OTH) AF: 0.230 AC: 13911 AN: 60396

GnomAD4 genome AF: 0.218 AC: 33100 AN: 152086 Hom.: 3906 Cov.: 33 AF XY: 0.216 AC XY: 16094 AN XY: 74346

African (AFR) AF: 0.151 AC: 6255 AN: 41488

American (AMR) AF: 0.214 AC: 3268 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3472

East Asian (EAS) AF: 0.101 AC: 524 AN: 5176

South Asian (SAS) AF: 0.161 AC: 775 AN: 4820

European-Finnish (FIN) AF: 0.294 AC: 3107 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17648 AN: 67952

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.242 Hom.: 3424

Bravo AF: 0.210

Asia WGS AF: 0.148 AC: 516 AN: 3478

EpiCase AF: 0.257

EpiControl AF: 0.254

ClinVar

ClinVar submissions

Significance: 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	-0.53
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.55
Mutation Taster		=93/7	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: rs2292195; hg19: chr11-6631016; COSMIC: COSV54989926; COSMIC: COSV54989926;