19-19188270-C-T

Variant names:

• chr19-19188270-C-T
• rs8100480
• NM_001145784.2:c.38-1265G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145784.2(BORCS8):​c.38-1265G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 152,048 control chromosomes in the GnomAD database, including 853 homozygotes. 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 0.085 (853 hom., cov: 32)
• Consequence: BORCS8 NM_001145784.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 6 publications found

Genes affected

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-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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS8	NM_001145784.2	c.38-1265G>A		intron_variant	Intron 1 of 5	ENST00000462790.8	NP_001139256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS8	ENST00000462790.8	c.38-1265G>A		intron_variant	Intron 1 of 5	1	NM_001145784.2	ENSP00000425864.1
BORCS8-MEF2B	ENST00000514819.7	c.-90+3811G>A		intron_variant	Intron 1 of 8	5		ENSP00000454967.3

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12939 AN: 151930 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0852 AC: 12948 AN: 152048 Hom.: 853 Cov.: 32 AF XY: 0.0854 AC XY: 6348 AN XY: 74334

African (AFR) AF: 0.151 AC: 6247 AN: 41462

American (AMR) AF: 0.0635 AC: 968 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1440 AN: 5134

South Asian (SAS) AF: 0.159 AC: 765 AN: 4822

European-Finnish (FIN) AF: 0.0261 AC: 277 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0421 AC: 2866 AN: 68002

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0239 Hom.: 17

Bravo AF: 0.0906

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs8100480; hg19: chr19-19299079;