rs759032416

Variant names:

• chr19-19145759-C-A
• rs759032416
• ENST00000514819.7:c.1084G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19145759-C-A
• chr19-19145759-C-G
• chr19-19145759-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000514819.7(BORCS8-MEF2B):​c.1084G>T​(p.Gly362Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,403,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G362S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BORCS8-MEF2B ENST00000514819.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• 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]

ACMG classification

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=0.12079713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2B	NM_001145785.2	c.*38G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000424583.7	NP_001139257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS8-MEF2B	ENST00000514819.7	c.1084G>T	p.Gly362Cys	missense_variant	Exon 9 of 9	5		ENSP00000454967.3
MEF2B	ENST00000424583.7	c.*38G>T		3_prime_UTR_variant	Exon 9 of 9	5	NM_001145785.2	ENSP00000402154.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000667 AC: 1 AN: 149966 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

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: 0.00000142 AC: 2 AN: 1403606 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 692686

African (AFR) AF: 0.00 AC: 0 AN: 32216

American (AMR) AF: 0.0000279 AC: 1 AN: 35850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 36766

South Asian (SAS) AF: 0.00 AC: 0 AN: 79628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081984

Other (OTH) AF: 0.0000172 AC: 1 AN: 58206

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000391 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	0.96
DANN	Benign	0.90
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.26	T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.32	T
PhyloP100		-0.51
PROVEAN	Benign	-1.6	N;.
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.017	D;D
Vest4		0.18
MutPred		0.17		Gain of catalytic residue at P344 (P = 0.0135);.;
MVP		0.19
MPC		0.39
ClinPred		0.14	T
GERP RS		0.0053
gMVP		0.024
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs759032416; hg19: chr19-19256568;