rs140322345

Variant names:

• chr11-6609311-C-T
• rs140322345
• NM_004517.4:c.631C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-6609311-C-T
• chr11-6609311-C-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R211H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: ILK NM_004517.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:7
• Conservation: PhyloP100: 5.36
• Publications: 10 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 -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 VariationId is 155799.
• BS2: High AC in GnomAd4 at 182 AD gene.

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.631C>T	p.Arg211Cys	missense	Exon 8 of 13	NP_004508.1	Q13418-1
	TAF10	NM_006284.4	MANE Select	c.*1611G>A		3_prime_UTR	Exon 5 of 5	NP_006275.1	Q12962
	ILK	NM_001014794.3		c.631C>T	p.Arg211Cys	missense	Exon 8 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.631C>T	p.Arg211Cys	missense	Exon 8 of 13	ENSP00000299421.4	Q13418-1
	ILK	ENST00000396751.6	TSL:1	c.631C>T	p.Arg211Cys	missense	Exon 7 of 12	ENSP00000379975.2	Q13418-1
	ILK	ENST00000420936.6	TSL:1	c.631C>T	p.Arg211Cys	missense	Exon 8 of 13	ENSP00000403487.2	Q13418-1

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 182 AN: 152154 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000955 AC: 240 AN: 251402 AF XY: 0.00102

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 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.: 0 Cov.: 34 AF XY: 0.00113 AC XY: 819 AN XY: 727208

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.00235 AC: 105 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53382

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00132 AC: 1469 AN: 1111930

Other (OTH) AF: 0.00113 AC: 68 AN: 60390

GnomAD4 genome AF: 0.00120 AC: 182 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74468

African (AFR) AF: 0.000217 AC: 9 AN: 41540

American (AMR) AF: 0.00386 AC: 59 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00148 AC: 101 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00125 Hom.: 2

Bravo AF: 0.00141

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.000840 AC: 102

EpiCase AF: 0.00196

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	1	1	not specified (2)
-	-	2	Primary familial hypertrophic cardiomyopathy (2)
-	-	1	ILK-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.026	T
MetaSVM	Uncertain	0.56	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.058	T
Polyphen		0.86	P
Vest4		0.64
MVP		0.97
MPC		1.1
ClinPred		0.060	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.72
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs140322345; hg19: chr11-6630542;