11-93784345-C-T

Variant names:

• chr11-93784345-C-T
• rs117654845
• NM_004268.5:c.-169C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004268.5(MED17):​c.-169C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 880,634 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (16 hom., cov: 33)
  • Exomes 𝑓: 0.016 (131 hom.)
• Consequence: MED17 NM_004268.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 3 publications found

Genes affected

MED17 (HGNC:2375): (mediator complex subunit 17) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. [provided by RefSeq, Jul 2008]

ENSG00000284057 (HGNC:):

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 11-93784345-C-T is Benign according to our data. Variant chr11-93784345-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0126 (1917/152340) while in subpopulation NFE AF = 0.0191 (1298/68032). AF 95% confidence interval is 0.0182. There are 16 homozygotes in GnomAd4. There are 907 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED17	NM_004268.5	c.-169C>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000251871.9	NP_004259.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED17	ENST00000251871.9	c.-169C>T		5_prime_UTR_variant	Exon 1 of 12	1	NM_004268.5	ENSP00000251871.3
ENSG00000284057	ENST00000638767.1	c.676-283C>T		intron_variant	Intron 7 of 18	5		ENSP00000492220.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1918 AN: 152222 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00487

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.0159 AC: 11556 AN: 728294 Hom.: 131 Cov.: 9 AF XY: 0.0155 AC XY: 5660 AN XY: 366124

African (AFR) AF: 0.00339 AC: 59 AN: 17386

American (AMR) AF: 0.0149 AC: 259 AN: 17414

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 191 AN: 15150

East Asian (EAS) AF: 0.00 AC: 0 AN: 31136

South Asian (SAS) AF: 0.00212 AC: 102 AN: 48090

European-Finnish (FIN) AF: 0.00267 AC: 79 AN: 29584

Middle Eastern (MID) AF: 0.00436 AC: 11 AN: 2522

European-Non Finnish (NFE) AF: 0.0195 AC: 10373 AN: 531960

Other (OTH) AF: 0.0138 AC: 482 AN: 35052

GnomAD4 genome AF: 0.0126 AC: 1917 AN: 152340 Hom.: 16 Cov.: 33 AF XY: 0.0122 AC XY: 907 AN XY: 74502

African (AFR) AF: 0.00486 AC: 202 AN: 41584

American (AMR) AF: 0.0178 AC: 272 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4828

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0191 AC: 1298 AN: 68032

Other (OTH) AF: 0.0180 AC: 38 AN: 2114

Alfa AF: 0.0161 Hom.: 2

Bravo AF: 0.0129

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 30, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.7
DANN	Benign	0.94
PhyloP100		-1.3
PromoterAI		0.0043	Neutral
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs117654845; hg19: chr11-93517511;