19-19145890-G-A

Variant names:

• chr19-19145890-G-A
• rs2060021038
• ENST00000514819.7:c.953C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000514819.7(BORCS8-MEF2B):​c.953C>T​(p.Pro318Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000305 in 1,312,380 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: BORCS8-MEF2B ENST00000514819.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.637
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049191564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2B	NM_001145785.2	c.1014C>T	p.Pro338Pro	synonymous_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.953C>T	p.Pro318Leu	missense_variant	Exon 9 of 9	5		ENSP00000454967.3
MEF2B	ENST00000424583.7	c.1014C>T	p.Pro338Pro	synonymous_variant	Exon 9 of 9	5	NM_001145785.2	ENSP00000402154.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000305 AC: 4 AN: 1312380 Hom.: 0 Cov.: 32 AF XY: 0.00000157 AC XY: 1 AN XY: 638498

African (AFR) AF: 0.00 AC: 0 AN: 28220

American (AMR) AF: 0.00 AC: 0 AN: 22182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19554

East Asian (EAS) AF: 0.00 AC: 0 AN: 34280

South Asian (SAS) AF: 0.00 AC: 0 AN: 66552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4810

European-Non Finnish (NFE) AF: 0.00000385 AC: 4 AN: 1038498

Other (OTH) AF: 0.00 AC: 0 AN: 54046

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.902C>T (p.P301L) 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 902, causing the proline (P) at amino acid position 301 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
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	8.0
DANN	Uncertain	0.99
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.35	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.67	T
PhyloP100		-0.64
PROVEAN	Benign	-0.33	N;.
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.034	D;D
Vest4		0.045
MutPred		0.15		Gain of catalytic residue at P301 (P = 0.0295);.;
MVP		0.23
MPC		0.38
ClinPred		0.30	T
GERP RS		0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
gMVP		0.069
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2060021038; hg19: chr19-19256699;