ENST00000638767.1:c.676-367C>T

Variant names:

• chr11-93784261-C-T
• rs74691257
• ENST00000638767.1:c.676-367C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000638767.1(ENSG00000284057):​c.676-367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00791 in 550,434 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (80 hom.)
• Consequence: ENSG00000284057 ENST00000638767.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04
• Publications: 3 publications found

Genes affected

ENSG00000284057 (HGNC:):

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]

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=-0.77).
• BP6: Variant 11-93784261-C-T is Benign according to our data. Variant chr11-93784261-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1211367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638767.1. 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
	MED17	NM_004268.5	MANE Select	c.-253C>T		upstream_gene	N/A	NP_004259.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000284057	ENST00000638767.1	TSL:5	c.676-367C>T		intron	N/A	ENSP00000492220.1	A0A1W2PRB8
	MED17	ENST00000920582.1		c.-253C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000590641.1
	MED17	ENST00000920582.1		c.-253C>T		5_prime_UTR	Exon 1 of 12	ENSP00000590641.1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1723 AN: 152186 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00660 AC: 2628 AN: 398130 Hom.: 80 Cov.: 4 AF XY: 0.00605 AC XY: 1251 AN XY: 206842

African (AFR) AF: 0.0308 AC: 336 AN: 10926

American (AMR) AF: 0.00293 AC: 40 AN: 13640

Ashkenazi Jewish (ASJ) AF: 0.000160 AC: 2 AN: 12510

East Asian (EAS) AF: 0.0751 AC: 2065 AN: 27514

South Asian (SAS) AF: 0.000884 AC: 30 AN: 33942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27482

Middle Eastern (MID) AF: 0.00223 AC: 4 AN: 1796

European-Non Finnish (NFE) AF: 0.000126 AC: 31 AN: 246740

Other (OTH) AF: 0.00509 AC: 120 AN: 23580

GnomAD4 genome AF: 0.0113 AC: 1726 AN: 152304 Hom.: 36 Cov.: 32 AF XY: 0.0114 AC XY: 851 AN XY: 74472

African (AFR) AF: 0.0313 AC: 1299 AN: 41562

American (AMR) AF: 0.00588 AC: 90 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0570 AC: 295 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68018

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.00527 Hom.: 3

Bravo AF: 0.0135

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		-1.0
PromoterAI		0.033	Neutral
Mutation Taster		=295/5	polymorphism

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: rs74691257; hg19: chr11-93517427;