rs1043388

Variant names:

• chr11-6608435-C-T
• rs1043388
• NM_004517.4:c.297C>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.297C>T​(p.His99His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,042 control chromosomes in the GnomAD database, including 56,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6965 hom., cov: 33)
  • Exomes 𝑓: 0.26 (49101 hom.)
• Consequence: ILK NM_004517.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.00400
• Publications: 24 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=-0.55).
• BP6: Variant 11-6608435-C-T is Benign according to our data. Variant chr11-6608435-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILK	NM_004517.4	MANE Select	c.297C>T	p.His99His	synonymous	Exon 4 of 13	NP_004508.1
	TAF10	NM_006284.4	MANE Select	c.*2487G>A		3_prime_UTR	Exon 5 of 5	NP_006275.1
	ILK	NM_001278442.2		c.-106C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	NP_001265371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILK	ENST00000299421.9	TSL:1 MANE Select	c.297C>T	p.His99His	synonymous	Exon 4 of 13	ENSP00000299421.4
	ILK	ENST00000396751.6	TSL:1	c.297C>T	p.His99His	synonymous	Exon 3 of 12	ENSP00000379975.2
	ILK	ENST00000420936.6	TSL:1	c.297C>T	p.His99His	synonymous	Exon 4 of 13	ENSP00000403487.2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44778 AN: 151966 Hom.: 6947 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.262 AC: 65891 AN: 251440 AF XY: 0.260

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.342

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.257 AC: 375362 AN: 1460958 Hom.: 49101 Cov.: 36 AF XY: 0.256 AC XY: 185764 AN XY: 726820

African (AFR) AF: 0.384 AC: 12859 AN: 33452

American (AMR) AF: 0.209 AC: 9355 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7516 AN: 26130

East Asian (EAS) AF: 0.331 AC: 13129 AN: 39692

South Asian (SAS) AF: 0.230 AC: 19799 AN: 86244

European-Finnish (FIN) AF: 0.244 AC: 13040 AN: 53418

Middle Eastern (MID) AF: 0.277 AC: 1595 AN: 5764

European-Non Finnish (NFE) AF: 0.254 AC: 282070 AN: 1111178

Other (OTH) AF: 0.265 AC: 15999 AN: 60362

GnomAD4 genome AF: 0.295 AC: 44850 AN: 152084 Hom.: 6965 Cov.: 33 AF XY: 0.292 AC XY: 21691 AN XY: 74338

African (AFR) AF: 0.379 AC: 15698 AN: 41460

American (AMR) AF: 0.258 AC: 3940 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3472

East Asian (EAS) AF: 0.346 AC: 1791 AN: 5170

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4814

European-Finnish (FIN) AF: 0.243 AC: 2568 AN: 10566

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17604 AN: 67982

Other (OTH) AF: 0.289 AC: 612 AN: 2116

Alfa AF: 0.275 Hom.: 4129

Bravo AF: 0.299

Asia WGS AF: 0.275 AC: 958 AN: 3478

EpiCase AF: 0.254

EpiControl AF: 0.255

ClinVar

ClinVar submissions as Germline

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	-0.55
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		-0.0040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=297/3	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: rs1043388; hg19: chr11-6629665; COSMIC: COSV54448699; COSMIC: COSV54448699;