chr11-6607812-G-A

Variant names:

• chr11-6607812-G-A
• rs2255538
• ENST00000616342.1:n.3876C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006284.4(TAF10):​c.*3110C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 557,380 control chromosomes in the GnomAD database, including 16,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4344 hom., cov: 32)
  • Exomes 𝑓: 0.23 (11861 hom.)
• Consequence: TAF10 NM_006284.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0390
• Publications: 15 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-6607812-G-A is Benign according to our data. Variant chr11-6607812-G-A is described in ClinVar as [Benign]. Clinvar id is 1287701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF10	NM_006284.4	c.*3110C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000299424.9	NP_006275.1
ILK	NM_004517.4	c.90-234G>A		intron_variant	Intron 2 of 12	ENST00000299421.9	NP_004508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF10	ENST00000299424.9	c.*3110C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_006284.4	ENSP00000299424.4
ILK	ENST00000299421.9	c.90-234G>A		intron_variant	Intron 2 of 12	1	NM_004517.4	ENSP00000299421.4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35386 AN: 151980 Hom.: 4339 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.235 AC: 95207 AN: 405280 Hom.: 11861 Cov.: 3 AF XY: 0.231 AC XY: 49397 AN XY: 213460

African (AFR) AF: 0.194 AC: 2239 AN: 11562

American (AMR) AF: 0.232 AC: 4019 AN: 17302

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 3116 AN: 12596

East Asian (EAS) AF: 0.123 AC: 3341 AN: 27138

South Asian (SAS) AF: 0.159 AC: 7098 AN: 44756

European-Finnish (FIN) AF: 0.290 AC: 7182 AN: 24736

Middle Eastern (MID) AF: 0.205 AC: 359 AN: 1754

European-Non Finnish (NFE) AF: 0.258 AC: 62470 AN: 242002

Other (OTH) AF: 0.230 AC: 5383 AN: 23434

GnomAD4 genome AF: 0.233 AC: 35406 AN: 152100 Hom.: 4344 Cov.: 32 AF XY: 0.231 AC XY: 17188 AN XY: 74346

African (AFR) AF: 0.202 AC: 8395 AN: 41486

American (AMR) AF: 0.222 AC: 3393 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3468

East Asian (EAS) AF: 0.102 AC: 530 AN: 5174

South Asian (SAS) AF: 0.161 AC: 775 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3110 AN: 10576

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17656 AN: 67970

Other (OTH) AF: 0.233 AC: 494 AN: 2116

Alfa AF: 0.245 Hom.: 2227

Bravo AF: 0.227

Asia WGS AF: 0.151 AC: 527 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.45
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism (auto)

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: rs2255538; hg19: chr11-6629042;