Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000571589.6(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. 12/18 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
ENST00000571589.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P

MRTFB links:

ENSG00000305939 (HGNC:):

ENSG00000305939 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2672618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1441 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000571589.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MRTFB	NM_001308142.2	MANE Select	c.864C>A	p.His288Gln	missense	Exon 10 of 17	NP_001295071.1
MRTFB	NM_001365411.2		c.831C>A	p.His277Gln	missense	Exon 8 of 15	NP_001352340.1
MRTFB	NM_001365412.2		c.864C>A	p.His288Gln	missense	Exon 11 of 17	NP_001352341.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MRTFB	ENST00000571589.6	TSL:2 MANE Select	c.864C>A	p.His288Gln	missense	Exon 10 of 17	ENSP00000459626.2
MRTFB	ENST00000574045.5	TSL:1	c.864C>A	p.His288Gln	missense	Exon 10 of 17	ENSP00000459205.1
MRTFB	ENST00000573051.1	TSL:1	c.711C>A	p.His237Gln	missense	Exon 8 of 9	ENSP00000460589.1

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

GnomAD2 exomes

AF:

0.00995

AC:

2460

AN:

247278

AF XY:

0.0102

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 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

African (AFR)

AF:

0.00207

AC:

AN:

33340

American (AMR)

AF:

0.00602

AC:

266

AN:

44194

Ashkenazi Jewish (ASJ)

AF:

0.00630

AC:

164

AN:

26028

East Asian (EAS)

AF:

0.000151

AC:

AN:

39662

South Asian (SAS)

AF:

0.00835

AC:

714

AN:

85474

European-Finnish (FIN)

AF:

0.00990

AC:

528

AN:

53330

Middle Eastern (MID)

AF:

0.00435

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0141

AC:

15636

AN:

1110758

Other (OTH)

AF:

0.00985

AC:

594

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

945

1890

2834

3779

4724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00947

AC:

1441

AN:

152202

Hom.:

Cov.:

AF XY:

0.00899

AC XY:

669

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00248

AC:

103

AN:

41528

American (AMR)

AF:

0.00903

AC:

138

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00664

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00643

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00793

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0151

AC:

1024

AN:

68004

Other (OTH)

AF:

0.00995

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0138

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.013

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0076

MetaSVM

Benign

-0.90

PhyloP100

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.46

REVEL

Benign

0.18

Sift

Benign

0.75

Sift4G

Benign

0.88

Polyphen

1.0

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

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs75963814

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over