NM_014815.4:c.2142T>C

Variant names:

• chr17-40023239-A-G
• rs2302777
• NM_014815.4:c.2142T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014815.4(MED24):​c.2142T>C​(p.Ile714Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,613,750 control chromosomes in the GnomAD database, including 116,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8378 hom., cov: 32)
  • Exomes 𝑓: 0.38 (108070 hom.)
• Consequence: MED24 NM_014815.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.417
• Publications: 53 publications found

Genes affected

MED24 (HGNC:22963): (mediator complex subunit 24) This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-40023239-A-G is Benign according to our data. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40023239-A-G is described in CliVar as Benign. Clinvar id is 1221841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.417 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED24	NM_014815.4	c.2142T>C	p.Ile714Ile	synonymous_variant	Exon 20 of 26	ENST00000394128.7	NP_055630.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7	c.2142T>C	p.Ile714Ile	synonymous_variant	Exon 20 of 26	1	NM_014815.4	ENSP00000377686.2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46261 AN: 151886 Hom.: 8385 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.393 AC: 98585 AN: 251102 AF XY: 0.401

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.415

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.380 AC: 554859 AN: 1461746 Hom.: 108070 Cov.: 68 AF XY: 0.384 AC XY: 279357 AN XY: 727182

African (AFR) AF: 0.0879 AC: 2942 AN: 33478

American (AMR) AF: 0.488 AC: 21818 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 11076 AN: 26124

East Asian (EAS) AF: 0.369 AC: 14646 AN: 39678

South Asian (SAS) AF: 0.483 AC: 41673 AN: 86250

European-Finnish (FIN) AF: 0.332 AC: 17709 AN: 53418

Middle Eastern (MID) AF: 0.511 AC: 2944 AN: 5766

European-Non Finnish (NFE) AF: 0.377 AC: 419248 AN: 1111938

Other (OTH) AF: 0.378 AC: 22803 AN: 60392

GnomAD4 genome AF: 0.304 AC: 46250 AN: 152004 Hom.: 8378 Cov.: 32 AF XY: 0.306 AC XY: 22739 AN XY: 74304

African (AFR) AF: 0.101 AC: 4176 AN: 41464

American (AMR) AF: 0.397 AC: 6064 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2131 AN: 5152

South Asian (SAS) AF: 0.471 AC: 2265 AN: 4810

European-Finnish (FIN) AF: 0.324 AC: 3426 AN: 10586

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25535 AN: 67930

Other (OTH) AF: 0.362 AC: 765 AN: 2114

Alfa AF: 0.357 Hom.: 18590

Bravo AF: 0.304

Asia WGS AF: 0.424 AC: 1478 AN: 3478

EpiCase AF: 0.406

EpiControl AF: 0.393

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 16, 2019

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	-0.69
CADD	Benign	5.9
DANN	Benign	0.78
PhyloP100		-0.42
PromoterAI		0.034	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2302777; hg19: chr17-38179492; COSMIC: COSV62416872; COSMIC: COSV62416872;