Variant 19-49836291-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030973.4(MED25):c.2031G>A(p.Ala677=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00967 in 1,611,934 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 93 hom. )

Consequence

MED25
NM_030973.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.73

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 19-49836291-G-A is Benign according to our data. Variant chr19-49836291-G-A is described in ClinVar as [Benign]. Clinvar id is 138200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49836291-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2172/152208) while in subpopulation AFR AF= 0.0285 (1182/41540). AF 95% confidence interval is 0.0271. There are 24 homozygotes in gnomad4. There are 965 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED25	NM_030973.4 linkuse as main transcript	c.2031G>A	p.Ala677=	synonymous_variant	17/18	ENST00000312865.10
MED25	NM_001378355.1 linkuse as main transcript	c.2031G>A	p.Ala677=	synonymous_variant	17/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED25	ENST00000312865.10 linkuse as main transcript	c.2031G>A	p.Ala677=	synonymous_variant	17/18	1	NM_030973.4		Q71SY5-1

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2167

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0284

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00958

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00817

AC:

1965

AN:

240568

Hom.:

AF XY:

0.00765

AC XY:

1011

AN XY:

132112

show subpopulations

Gnomad AFR exome

AF:

0.0306

Gnomad AMR exome

AF:

0.00754

Gnomad ASJ exome

AF:

0.00951

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00135

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00960

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00919

AC:

13412

AN:

1459726

Hom.:

Cov.:

AF XY:

0.00892

AC XY:

6479

AN XY:

726146

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.00753

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.00215

Gnomad4 NFE exome

AF:

0.00973

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.0143

AC:

2172

AN:

152208

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

965

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0285

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00958

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00889

EpiControl

AF:

0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Charcot-Marie-Tooth disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.0

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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