dbSNP rs566625799: BORCS8-MEF2B:c.-46G>C (chr19-19182640-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005919.4(BORCS8-MEF2B):c.-173G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Consequence

BORCS8-MEF2B
NM_005919.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.43

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:

BORCS8 (HGNC:37247): (BLOC-1 related complex subunit 8) Involved in heart development. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS8 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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14813563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS8	NM_001145784.2 link	c.259G>C	p.Val87Leu	missense_variant	Exon 4 of 6	ENST00000462790.8	NP_001139256.1	Q96FH0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BORCS8-MEF2B	ENST00000514819.7 link	c.-46G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	5		ENSP00000454967.3	H3BNR1
BORCS8	ENST00000462790.8 link	c.259G>C	p.Val87Leu	missense_variant	Exon 4 of 6	1	NM_001145784.2	ENSP00000425864.1	Q96FH0-1
BORCS8-MEF2B	ENST00000514819.7 link	c.-46G>C		5_prime_UTR_variant	Exon 2 of 9	5		ENSP00000454967.3	H3BNR1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000653

AC:

AN:

153078

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000420

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.054

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.2

N;.;N

REVEL

Benign

0.14

Sift

Uncertain

0.023

D;.;D

Sift4G

Benign

0.096

T;D;T

Polyphen

0.062

B;.;B

Vest4

0.44

MutPred

0.63

Loss of methylation at K92 (P = 0.0719);.;Loss of methylation at K92 (P = 0.0719);

MVP

0.067

ClinPred

0.52

GERP RS

2.9

Varity_R

0.084

gMVP

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over