rs7249142

Positions:

• chr19-19165550-A-G
• chr19-19165550-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145785.2(MEF2B):​c.-30+4655T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,934 control chromosomes in the GnomAD database, including 32,999 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 0.65 (32999 hom., cov: 31)
• Consequence: MEF2B NM_001145785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

Genes affected

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]

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-MEF2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2B	NM_001145785.2	c.-30+4655T>C		intron_variant		ENST00000424583.7	NP_001139257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2B	ENST00000424583.7	c.-30+4655T>C		intron_variant		5	NM_001145785.2	ENSP00000402154.2
BORCS8-MEF2B	ENST00000514819.7	c.23-14786T>C		intron_variant		5		ENSP00000454967.3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99048 AN: 151816 Hom.: 32954 Cov.: 31

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.653 AC: 99151 AN: 151934 Hom.: 32999 Cov.: 31 AF XY: 0.651 AC XY: 48350 AN XY: 74242

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.570

Alfa AF: 0.603 Hom.: 36600

Bravo AF: 0.657

Asia WGS AF: 0.677 AC: 2355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.94
DANN	Benign	0.59

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: rs7249142; hg19: chr19-19276359;