Variant 16-14240269-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001308142.2(MRTFB):c.864C>A(p.His288Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,611,022 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 9 hom., cov: 33)

Exomes 𝑓: 0.012 ( 141 hom. )

Consequence

MRTFB
NM_001308142.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

MRTFB (HGNC:29819): (myocardin related transcription factor B) Enables transcription coactivator activity. Involved in positive regulation of pri-miRNA transcription by RNA polymerase II and positive regulation of striated muscle tissue development. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MRTFB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007615596).

BP6

Variant 16-14240269-C-A is Benign according to our data. Variant chr16-14240269-C-A is described in ClinVar as [Benign]. Clinvar id is 2672618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRTFB	NM_001308142.2 linkuse as main transcript	c.864C>A	p.His288Gln	missense_variant	10/17	ENST00000571589.6	NP_001295071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRTFB	ENST00000571589.6 linkuse as main transcript	c.864C>A	p.His288Gln	missense_variant	10/17	2	NM_001308142.2	ENSP00000459626	P4	Q9ULH7-5

Frequencies

GnomAD3 genomes

AF:

0.00948

AC:

1442

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00904

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.00793

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00995

AC:

2460

AN:

247278

Hom.:

AF XY:

0.0102

AC XY:

1362

AN XY:

133636

show subpopulations

Gnomad AFR exome

AF:

0.00211

Gnomad AMR exome

AF:

0.00505

Gnomad ASJ exome

AF:

0.00597

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00889

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.00894

GnomAD4 exome

AF:

0.0123

AC:

18002

AN:

1458820

Hom.:

141

Cov.:

AF XY:

0.0123

AC XY:

8953

AN XY:

725368

show subpopulations

Gnomad4 AFR exome

AF:

0.00207

Gnomad4 AMR exome

AF:

0.00602

Gnomad4 ASJ exome

AF:

0.00630

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00835

Gnomad4 FIN exome

AF:

0.00990

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.00985

GnomAD4 genome

AF:

0.00947

AC:

1441

AN:

152202

Hom.:

Cov.:

AF XY:

0.00899

AC XY:

669

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.00903

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.00793

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.00877

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0158

AC:

136

ExAC

AF:

0.0101

AC:

1221

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0134

EpiControl

AF:

0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

MRTFB: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.013

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

D;.;D;D;D

MetaRNN

Benign

0.0076

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.46

.;.;N;.;.

REVEL

Benign

0.18

Sift

Benign

0.75

.;.;T;.;.

Sift4G

Benign

0.88

T;T;T;T;.

Polyphen

1.0, 0.95

.;D;D;.;P

Vest4

0.51

MutPred

0.070

.;.;.;Gain of methylation at K280 (P = 0.1087);.;

MPC

0.43

ClinPred

0.024

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.48

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