rs369618700

Variant names:

• chr19-19182679-C-G
• rs369618700
• ENST00000514819.7:c.-85G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-19182679-C-G
• chr19-19182679-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005919.4(BORCS8-MEF2B):​c.-212G>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 0.00000143 in 1,397,922 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BORCS8-MEF2B NM_005919.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

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

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]

ACMG classification

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=0.24320173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS8	NM_001145784.2	c.220G>C	p.Val74Leu	missense_variant	Exon 4 of 6	ENST00000462790.8	NP_001139256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS8-MEF2B	ENST00000514819.7	c.-85G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	5		ENSP00000454967.3
BORCS8	ENST00000462790.8	c.220G>C	p.Val74Leu	missense_variant	Exon 4 of 6	1	NM_001145784.2	ENSP00000425864.1
BORCS8-MEF2B	ENST00000514819.7	c.-85G>C		5_prime_UTR_variant	Exon 2 of 9	5		ENSP00000454967.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397922 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 689468

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T;D;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N;.;N
REVEL	Benign	0.14
Sift	Benign	0.34	T;.;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.37	B;.;B
Vest4		0.53
MutPred		0.69		Loss of methylation at K75 (P = 0.0374);.;Loss of methylation at K75 (P = 0.0374);
MVP		0.067
ClinPred		0.28	T
GERP RS		3.0
Varity_R		0.079
gMVP		0.78

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

Other links and lift over

dbSNP: rs369618700; hg19: chr19-19293488;