ENST00000514819.7:c.883C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000514819.7(BORCS8-MEF2B):c.883C>T(p.Gln295*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,440,380 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

BORCS8-MEF2B
ENST00000514819.7 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.622

Publications

1 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2B	NM_001145785.2 link	c.944C>T	p.Pro315Leu	missense_variant	Exon 9 of 9	ENST00000424583.7	NP_001139257.1	Q02080-2A0A024R7K5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS8-MEF2B	ENST00000514819.7 link	c.883C>T	p.Gln295*	stop_gained	Exon 9 of 9	5		ENSP00000454967.3		H3BNR1
MEF2B	ENST00000424583.7 link	c.944C>T	p.Pro315Leu	missense_variant	Exon 9 of 9	5	NM_001145785.2	ENSP00000402154.2		Q02080-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000208

AC:

AN:

48130

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000361

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:

0.00000699

AC:

AN:

1288102

Hom.:

Cov.:

AF XY:

0.00000798

AC XY:

AN XY:

626320

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26302

American (AMR)

AF:

0.00

AC:

AN:

18374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18420

East Asian (EAS)

AF:

0.00

AC:

AN:

32076

South Asian (SAS)

AF:

0.0000637

AC:

AN:

62804

European-Finnish (FIN)

AF:

0.0000239

AC:

AN:

41874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3966

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1031348

Other (OTH)

AF:

0.0000567

AC:

AN:

52938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41588

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.944C>T (p.P315L) alteration is located in exon 9 (coding exon 8) of the MEF2B gene. This alteration results from a C to T substitution at nucleotide position 944, causing the proline (P) at amino acid position 315 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;.;T

Eigen

Benign

0.11

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.62

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.94

N;N;.

REVEL

Benign

0.081

Sift

Benign

0.039

D;D;.

Sift4G

Benign

0.29

T;T;T

Polyphen

0.099

.;B;.

Vest4

0.20

MutPred

0.24

.;Gain of sheet (P = 0.0149);.;

MVP

0.50

ClinPred

0.23

GERP RS

2.1

Mutation Taster

=91/109

disease causing

(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

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ENST00000514819.7:c.883C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over