chr19-19175268-C-T

Variant names:

• chr19-19175268-C-T
• rs11671119
• ENST00000514819.7:c.22+7305G>A

Variant summary

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

The ENST00000514819.7(BORCS8-MEF2B):​c.22+7305G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 152,308 control chromosomes in the GnomAD database, including 274 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 0.039 (274 hom., cov: 32)
• Consequence: BORCS8-MEF2B ENST00000514819.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS8-MEF2B	NM_005919.4	c.-30+5418G>A		intron_variant	Intron 3 of 9		NP_005910.1
BORCS8-MEF2B	NR_027307.2	n.437+5418G>A		intron_variant	Intron 5 of 12
BORCS8-MEF2B	NR_027308.2	n.437+5418G>A		intron_variant	Intron 5 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS8-MEF2B	ENST00000514819.7	c.22+7305G>A		intron_variant	Intron 2 of 8	5		ENSP00000454967.3

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5971 AN: 152190 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0391 AC: 5962 AN: 152308 Hom.: 274 Cov.: 32 AF XY: 0.0399 AC XY: 2973 AN XY: 74466

African (AFR) AF: 0.0247 AC: 1027 AN: 41568

American (AMR) AF: 0.0412 AC: 630 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1303 AN: 5172

South Asian (SAS) AF: 0.105 AC: 508 AN: 4824

European-Finnish (FIN) AF: 0.0146 AC: 155 AN: 10622

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0306 AC: 2085 AN: 68036

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0303 Hom.: 54

Bravo AF: 0.0400

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.011
DANN	Benign	0.78
PhyloP100		-3.9

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: rs11671119; hg19: chr19-19286077;