ENST00000514819.7:c.932C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000514819.7(BORCS8-MEF2B):c.932C>T(p.Ala311Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,443,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

BORCS8-MEF2B
ENST00000514819.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25

Publications

0 publications found

Variant links:

Genes affected

BORCS8-MEF2B (HGNC:39979): (BORCS8-MEF2B readthrough) This gene represents numerous read-through transcripts that span GeneID:729991 and 100271849. Many read-through transcripts are predicted to be nonsense-mediated decay (NMD) candidates, and are thought to be non-coding. Some transcripts are predicted to be capable of translation reinitiation at a downstream AUG, resulting in expression of at least one isoform of myocyte enhancer factor 2B (MEF2B) from this read-through locus. At least one additional MEF2B variant and isoform can be expressed from a downstream promoter, and is annotated on GeneID:100271849. [provided by RefSeq, Oct 2010]

BORCS8-MEF2B links:

MEF2B (HGNC:6995): (myocyte enhancer factor 2B) The product of this gene is a member of the MADS/MEF2 family of DNA binding proteins. The protein is thought to regulate gene expression, including expression of the smooth muscle myosin heavy chain gene. This region undergoes considerable alternative splicing, with transcripts supporting two non-overlapping loci (GeneID 729991 and 100271849) as well as numerous read-through transcripts that span both loci (annotated as GeneID 4207). Several isoforms of this protein are expressed from either this locus or from some of the read-through transcripts annotated on GeneID 4207. [provided by RefSeq, Jan 2014]

MEF2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038873702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514819.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEF2B	NM_001145785.2	MANE Select	c.993C>T	p.Gly331Gly	synonymous	Exon 9 of 9	NP_001139257.1	Q02080-2
MEF2B	NM_001367282.1		c.881C>T	p.Ala294Val	missense	Exon 8 of 8	NP_001354211.1	Q02080-1
BORCS8-MEF2B	NM_005919.4		c.881C>T	p.Ala294Val	missense	Exon 10 of 10	NP_005910.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BORCS8-MEF2B	ENST00000514819.7	TSL:5	c.932C>T	p.Ala311Val	missense	Exon 9 of 9	ENSP00000454967.3	H3BNR1
MEF2B	ENST00000424583.7	TSL:5 MANE Select	c.993C>T	p.Gly331Gly	synonymous	Exon 9 of 9	ENSP00000402154.2	Q02080-2
MEF2B	ENST00000444486.7	TSL:2	c.881C>T	p.Ala294Val	missense	Exon 10 of 10	ENSP00000390762.2	Q02080-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

55848

AF XY:

0.0000346

show subpopulations

Gnomad AFR exome

AF:

0.000580

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000465

AC:

AN:

1290804

Hom.:

Cov.:

AF XY:

0.00000319

AC XY:

AN XY:

626210

show subpopulations

African (AFR)

AF:

0.000223

AC:

AN:

26846

American (AMR)

AF:

0.00

AC:

AN:

19166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18624

East Asian (EAS)

AF:

0.00

AC:

AN:

32556

South Asian (SAS)

AF:

0.00

AC:

AN:

63526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4474

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1029104

Other (OTH)

AF:

0.00

AC:

AN:

53064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Benign

4.4

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.31

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.83

PhyloP100

-1.3

PROVEAN

Benign

0.060

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Benign

0.63

Vest4

0.041

MutPred

0.15

Gain of sheet (P = 0.0149)

MVP

0.18

MPC

0.37

ClinPred

0.045

GERP RS

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.075

Mutation Taster

=98/2

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.

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