Variant 13-48077193-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014166.4(MED4):c.759T>A(p.Asp253Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,608,846 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 15 hom. )

Consequence

MED4
NM_014166.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.823

Variant links:

Genes affected

MED4 (HGNC:17903): (mediator complex subunit 4) This gene encodes a component of the Mediator complex. The Mediator complex interacts with DNA-binding gene-specific transcription factors to modulate transcription by RNA polymerase II. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

MED4 links:

MED4-AS1 (HGNC:39213): (MED4 antisense RNA 1)

MED4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00830999).

BP6

Variant 13-48077193-A-T is Benign according to our data. Variant chr13-48077193-A-T is described in ClinVar as [Benign]. Clinvar id is 773271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MED4	NM_014166.4 linkuse as main transcript	c.759T>A	p.Asp253Glu	missense_variant	7/7	ENST00000258648.7	NP_054885.1
MED4-AS1	NR_046511.1 linkuse as main transcript	n.57A>T		non_coding_transcript_exon_variant	1/3
MED4	NM_001270629.2 linkuse as main transcript	c.621T>A	p.Asp207Glu	missense_variant	7/7		NP_001257558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED4	ENST00000258648.7 linkuse as main transcript	c.759T>A	p.Asp253Glu	missense_variant	7/7	1	NM_014166.4	ENSP00000258648	P1	Q9NPJ6-1
MED4-AS1	ENST00000422483.1 linkuse as main transcript	n.57A>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

457

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00303

AC:

741

AN:

244486

Hom.:

AF XY:

0.00294

AC XY:

389

AN XY:

132338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00395

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000342

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.00285

Gnomad OTH exome

AF:

0.00420

GnomAD4 exome

AF:

0.00251

AC:

3661

AN:

1456560

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1827

AN XY:

724612

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.00442

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00300

AC:

457

AN:

152286

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00169

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00282

AC:

342

Asia WGS

AF:

0.000578

AC:

AN:

3476

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.048

T;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

N;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.27

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.35

T;T;.

Polyphen

0.0020

B;.;.

Vest4

0.31

MutPred

0.51

Loss of stability (P = 0.1053);.;.;

MVP

0.41

MPC

0.33

ClinPred

0.032

GERP RS

2.0

Varity_R

0.053

gMVP

0.18

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