Genetic Variant MRTFB:c.2765-105A>G (chr16-14260804-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001308142.2(MRTFB):c.2765-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 925,622 control chromosomes in the GnomAD database, including 12,950 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 5258 hom., cov: 33)

Exomes 𝑓: 0.12 ( 7692 hom. )

Consequence

MRTFB
NM_001308142.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308142.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRTFB	NM_001308142.2	MANE Select	c.2765-105A>G	intron	N/A	NP_001295071.1
MRTFB	NM_001365411.2		c.2732-105A>G	intron	N/A	NP_001352340.1
MRTFB	NM_001365412.2		c.2627-105A>G	intron	N/A	NP_001352341.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRTFB	ENST00000571589.6	TSL:2 MANE Select	c.2765-105A>G	intron	N/A	ENSP00000459626.2
MRTFB	ENST00000574045.5	TSL:1	c.2615-105A>G	intron	N/A	ENSP00000459205.1
MRTFB	ENST00000572588.1	TSL:1	n.2033-105A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31084

AN:

152090

Hom.:

5233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.0840

Gnomad OTH

AF:

0.206

GnomAD4 exome

AF:

0.115

AC:

89275

AN:

773412

Hom.:

7692

AF XY:

0.118

AC XY:

46598

AN XY:

395492

show subpopulations

African (AFR)

AF:

0.463

AC:

8300

AN:

17928

American (AMR)

AF:

0.145

AC:

3462

AN:

23954

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

1967

AN:

16210

East Asian (EAS)

AF:

0.310

AC:

10236

AN:

33040

South Asian (SAS)

AF:

0.201

AC:

10695

AN:

53098

European-Finnish (FIN)

AF:

0.0578

AC:

2349

AN:

40642

Middle Eastern (MID)

AF:

0.199

AC:

773

AN:

3880

European-Non Finnish (NFE)

AF:

0.0845

AC:

46324

AN:

548138

Other (OTH)

AF:

0.142

AC:

5169

AN:

36522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3778

7556

11333

15111

18889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1478

2956

4434

5912

7390

<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:

0.205

AC:

31172

AN:

152210

Hom.:

5258

Cov.:

AF XY:

0.204

AC XY:

15174

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.450

AC:

18692

AN:

41500

American (AMR)

AF:

0.161

AC:

2466

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

471

AN:

3470

East Asian (EAS)

AF:

0.302

AC:

1566

AN:

5186

South Asian (SAS)

AF:

0.213

AC:

1030

AN:

4826

European-Finnish (FIN)

AF:

0.0603

AC:

640

AN:

10614

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0840

AC:

5711

AN:

68006

Other (OTH)

AF:

0.206

AC:

436

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1089

2178

3267

4356

5445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.112

Hom.:

647

Bravo

AF:

0.223

Asia WGS

AF:

0.257

AC:

895

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.069

(source)

DANN

Benign

0.21

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Computational scores

Splicing

Publications

Other links and lift over