19-19175268-C-T

Variant summary

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

The NR_027308.2(BORCS8-MEF2B):n.437+5418G>A variant causes a intron, non coding transcript 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 NR_027308.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94

Genes affected

BORCS8-MEF2B (HGNC:):

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BORCS8-MEF2B	NR_027308.2	n.437+5418G>A		intron_variant, non_coding_transcript_variant
BORCS8-MEF2B	NM_005919.4	c.-30+5418G>A		intron_variant
BORCS8-MEF2B	NR_027307.2	n.437+5418G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2B	ENST00000444486.7	c.-30+5418G>A		intron_variant		2		A2

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

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0412

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0256 Hom.: 21

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

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: rs11671119; hg19: chr19-19286077;