NM_004268.5:c.-216A>C

Variant names:

• chr11-93784298-A-C
• rs16919375
• NM_004268.5:c.-216A>C

Variant summary

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

The NM_004268.5(MED17):​c.-216A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00589 in 630,810 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (87 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (27 hom.)
• Consequence: MED17 NM_004268.5 5_prime_UTR
• Scores: Splicing: ADA: 0.00005058
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.70
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-93784298-A-C is Benign according to our data. Variant chr11-93784298-A-C is described in ClinVar as [Benign]. Clinvar id is 1244461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED17	NM_004268.5	c.-216A>C		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.-216A>C		5_prime_UTR_variant	Exon 1 of 12	1	NM_004268.5	ENSP00000251871.3
ENSG00000284057	ENST00000638767.1	c.676-330A>C		intron_variant	Intron 7 of 18	5		ENSP00000492220.1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2674 AN: 152032 Hom.: 87 Cov.: 33

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00720

GnomAD4 exome AF: 0.00215 AC: 1028 AN: 478660 Hom.: 27 Cov.: 6 AF XY: 0.00189 AC XY: 468 AN XY: 247440

African (AFR) AF: 0.0638 AC: 795 AN: 12466

American (AMR) AF: 0.00359 AC: 56 AN: 15618

Ashkenazi Jewish (ASJ) AF: 0.0000742 AC: 1 AN: 13480

East Asian (EAS) AF: 0.00 AC: 0 AN: 29304

South Asian (SAS) AF: 0.000225 AC: 9 AN: 40030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28940

Middle Eastern (MID) AF: 0.00501 AC: 10 AN: 1998

European-Non Finnish (NFE) AF: 0.0000967 AC: 30 AN: 310080

Other (OTH) AF: 0.00475 AC: 127 AN: 26744

GnomAD4 genome AF: 0.0176 AC: 2685 AN: 152150 Hom.: 87 Cov.: 33 AF XY: 0.0166 AC XY: 1233 AN XY: 74374

African (AFR) AF: 0.0619 AC: 2570 AN: 41494

American (AMR) AF: 0.00556 AC: 85 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68020

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.00710 Hom.: 39

Bravo AF: 0.0198

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 26, 2018

GeneDx

Significance: 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	-0.82
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		-1.7
PromoterAI		-0.017	Neutral
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000051
dbscSNV1_RF	Benign	0.0020
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: rs16919375; hg19: chr11-93517464;