Variant chr17-40023239-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014815.4(MED24):c.2142T>C(p.Ile714=) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.417

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	UniProt
MED24	NM_014815.4 linkuse as main transcript	c.2142T>C	p.Ile714=	synonymous_variant	20/26	ENST00000394128.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED24	ENST00000394128.7 linkuse as main transcript	c.2142T>C	p.Ile714=	synonymous_variant	20/26	1	NM_014815.4	P1	O75448-1

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46261

AN:

151886

Hom.:

8385

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.393

AC:

98585

AN:

251102

Hom.:

20668

AF XY:

0.401

AC XY:

54375

AN XY:

135732

show subpopulations

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 SAS exome

AF:

0.481

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.:

AF XY:

0.384

AC XY:

279357

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0879

Gnomad4 AMR exome

AF:

0.488

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.369

Gnomad4 SAS exome

AF:

0.483

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.304

AC:

46250

AN:

152004

Hom.:

8378

Cov.:

AF XY:

0.306

AC XY:

22739

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.414

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.373

Hom.:

14669

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

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	Jul 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.9

DANN

Benign

0.78

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

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