Variant 19-49835196-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000312865.10(MED25):c.1674+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,184 control chromosomes in the GnomAD database, including 16,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1061 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14997 hom. )

Consequence

MED25
ENST00000312865.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.688

Variant links:

Genes affected

MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]

MED25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 19-49835196-C-T is Benign according to our data. Variant chr19-49835196-C-T is described in ClinVar as [Benign]. Clinvar id is 138199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49835196-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED25	NM_030973.4 linkuse as main transcript	c.1674+19C>T		intron_variant		ENST00000312865.10	NP_112235.2
MED25	NM_001378355.1 linkuse as main transcript	c.1674+19C>T		intron_variant			NP_001365284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED25	ENST00000312865.10 linkuse as main transcript	c.1674+19C>T		intron_variant		1	NM_030973.4	ENSP00000326767		Q71SY5-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17067

AN:

151988

Hom.:

1061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0675

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.117

AC:

29298

AN:

251098

Hom.:

1887

AF XY:

0.118

AC XY:

16019

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.0683

Gnomad AMR exome

AF:

0.0741

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.0775

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.139

AC:

203535

AN:

1461078

Hom.:

14997

Cov.:

AF XY:

0.138

AC XY:

100238

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.0673

Gnomad4 AMR exome

AF:

0.0783

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.0762

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.112

AC:

17065

AN:

152106

Hom.:

1061

Cov.:

AF XY:

0.110

AC XY:

8193

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0675

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0748

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.131

Hom.:

1597

Bravo

AF:

0.113

Asia WGS

AF:

0.0940

AC:

328

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Charcot-Marie-Tooth disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.5

DANN

Benign

0.72

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

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