Variant chr1-28334563-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017638.3(MED18):c.220C>T(p.Arg74Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000347 in 1,614,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

MED18
NM_017638.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.79

Variant links:

Genes affected

MED18 (HGNC:25944): (mediator complex subunit 18) MED18 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II (Sato et al., 2003 [PubMed 12584197]).[supplied by OMIM, Oct 2008]

MED18 links:

MED18 (HGNC:):

MED18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0178366).

BP6

Variant 1-28334563-C-T is Benign according to our data. Variant chr1-28334563-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713263.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED18	NM_017638.3 linkuse as main transcript	c.220C>T	p.Arg74Cys	missense_variant	3/3	ENST00000373842.9	NP_060108.2	Q9BUE0
MED18	NM_001127350.2 linkuse as main transcript	c.220C>T	p.Arg74Cys	missense_variant	3/3		NP_001120822.1	Q9BUE0
MED18	XM_005245914.5 linkuse as main transcript	c.220C>T	p.Arg74Cys	missense_variant	3/3		XP_005245971.1	Q9BUE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MED18	ENST00000373842.9 linkuse as main transcript	c.220C>T	p.Arg74Cys	missense_variant	3/3	2	NM_017638.3	ENSP00000362948.4	Q9BUE0
MED18	ENST00000398997.2 linkuse as main transcript	c.220C>T	p.Arg74Cys	missense_variant	3/4	5		ENSP00000381963.2	Q9BUE0
MED18	ENST00000474683.1 linkuse as main transcript	n.379C>T		non_coding_transcript_exon_variant	3/3	3
MED18	ENST00000479574.5 linkuse as main transcript	n.409C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

197

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000561

AC:

141

AN:

251474

Hom.:

AF XY:

0.000478

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00455

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

177

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00493

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000917

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152312

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00418

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000338

Hom.:

Bravo

AF:

0.00170

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000552

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.40

T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.013

MetaRNN

Benign

0.018

T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

0.85

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-4.3

D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.56

MVP

0.40

MPC

1.7

ClinPred

0.031

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.71

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