Variant 17-40019613-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014815.4(MED24):c.2886C>T(p.Ser962Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,605,232 control chromosomes in the GnomAD database, including 19,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1959 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17919 hom. )

Consequence

MED24
NM_014815.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.54

Variant links:

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]

MED24 links:

MED24 (HGNC:):

MED24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 17-40019613-G-A is Benign according to our data. Variant chr17-40019613-G-A is described in ClinVar as [Benign]. Clinvar id is 1266811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED24	NM_014815.4 linkuse as main transcript	c.2886C>T	p.Ser962Ser	synonymous_variant	26/26	ENST00000394128.7	NP_055630.2	O75448-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7 linkuse as main transcript	c.2886C>T	p.Ser962Ser	synonymous_variant	26/26	1	NM_014815.4	ENSP00000377686.2		O75448-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23142

AN:

152150

Hom.:

1959

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.0674

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.127

AC:

30957

AN:

244254

Hom.:

2335

AF XY:

0.125

AC XY:

16561

AN XY:

132210

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0791

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.00799

Gnomad SAS exome

AF:

0.0737

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.151

AC:

218975

AN:

1452964

Hom.:

17919

Cov.:

AF XY:

0.148

AC XY:

107207

AN XY:

721998

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0804

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.00359

Gnomad4 SAS exome

AF:

0.0722

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.152

AC:

23148

AN:

152268

Hom.:

1959

Cov.:

AF XY:

0.148

AC XY:

11030

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.00598

Gnomad4 SAS

AF:

0.0681

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.156

Hom.:

2453

Bravo

AF:

0.152

Asia WGS

AF:

0.0630

AC:

220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.6

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over