19-19165550-A-G

Variant names:

• chr19-19165550-A-G
• rs7249142
• NM_001145785.2:c.-30+4655T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145785.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2B	NM_001145785.2	MANE Select	c.-30+4655T>C		intron	N/A	NP_001139257.1
	MEF2B	NM_001367282.1		c.-30+4655T>C		intron	N/A	NP_001354211.1
	BORCS8-MEF2B	NM_005919.4		c.-29-14786T>C		intron	N/A	NP_005910.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2B	ENST00000424583.7	TSL:5 MANE Select	c.-30+4655T>C		intron	N/A	ENSP00000402154.2
	BORCS8-MEF2B	ENST00000514819.7	TSL:5	c.23-14786T>C		intron	N/A	ENSP00000454967.3
	MEF2B	ENST00000410050.5	TSL:5	c.-30+4655T>C		intron	N/A	ENSP00000386374.1

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

African (AFR) AF: 0.772 AC: 31967 AN: 41400

American (AMR) AF: 0.622 AC: 9490 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1962 AN: 3470

East Asian (EAS) AF: 0.744 AC: 3831 AN: 5152

South Asian (SAS) AF: 0.679 AC: 3264 AN: 4810

European-Finnish (FIN) AF: 0.583 AC: 6158 AN: 10560

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.597 AC: 40604 AN: 67960

Other (OTH) AF: 0.570 AC: 1205 AN: 2114

Alfa AF: 0.621 Hom.: 56833

Bravo AF: 0.657

Asia WGS AF: 0.677 AC: 2355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.94
DANN	Benign	0.59
PhyloP100		-0.50

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: rs7249142; hg19: chr19-19276359;