rs1178747030
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000514819.7(BORCS8-MEF2B):c.1070C>T(p.Pro357Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 1,552,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000079 ( 0 hom. )
Consequence
BORCS8-MEF2B
ENST00000514819.7 missense
ENST00000514819.7 missense
Scores
1
1
14
Clinical Significance
Conservation
PhyloP100: -1.14
Publications
1 publications found
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]
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.074599445).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MEF2B | NM_001145785.2 | c.*24C>T | 3_prime_UTR_variant | Exon 9 of 9 | ENST00000424583.7 | NP_001139257.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152178
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000785 AC: 11AN: 1400640Hom.: 0 Cov.: 32 AF XY: 0.0000101 AC XY: 7AN XY: 690810 show subpopulations
GnomAD4 exome
AF:
AC:
11
AN:
1400640
Hom.:
Cov.:
32
AF XY:
AC XY:
7
AN XY:
690810
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32052
American (AMR)
AF:
AC:
0
AN:
35578
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25120
East Asian (EAS)
AF:
AC:
0
AN:
36506
South Asian (SAS)
AF:
AC:
0
AN:
79506
European-Finnish (FIN)
AF:
AC:
0
AN:
48024
Middle Eastern (MID)
AF:
AC:
0
AN:
5662
European-Non Finnish (NFE)
AF:
AC:
11
AN:
1080146
Other (OTH)
AF:
AC:
0
AN:
58046
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152178
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74340
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41446
American (AMR)
AF:
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5168
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68018
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Dec 21, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1019C>T (p.P340L) alteration is located in exon 10 (coding exon 7) of the BORCS8-MEF2B gene. This alteration results from a C to T substitution at nucleotide position 1019, causing the proline (P) at amino acid position 340 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PhyloP100
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Pathogenic
D;.
Sift4G
Benign
T;T
Vest4
MutPred
Loss of glycosylation at P340 (P = 0.0349);.;
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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