19-19147124-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001145785.2(MEF2B):c.453C>A(p.Gly151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,604,790 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (31 hom.)
• Consequence: MEF2B NM_001145785.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.91

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:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 19-19147124-G-T is Benign according to our data. Variant chr19-19147124-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 788835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.91 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2B	NM_001145785.2	c.453C>A	p.Gly151=	synonymous_variant	5/9	ENST00000424583.7
BORCS8-MEF2B	NR_027308.2	n.919C>A		non_coding_transcript_exon_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2B	ENST00000424583.7	c.453C>A	p.Gly151=	synonymous_variant	5/9	5	NM_001145785.2	P4

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 671 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00682

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00416 AC: 951 AN: 228342 Hom.: 2 AF XY: 0.00399 AC XY: 496 AN XY: 124286

Gnomad AFR exome AF: 0.000828

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.0000577

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00499

Gnomad NFE exome AF: 0.00723

Gnomad OTH exome AF: 0.00428

GnomAD4 exome AF: 0.00600 AC: 8715 AN: 1452464 Hom.: 31 Cov.: 32 AF XY: 0.00586 AC XY: 4233 AN XY: 721992

Gnomad4 AFR exome AF: 0.000631

Gnomad4 AMR exome AF: 0.00117

Gnomad4 ASJ exome AF: 0.000387

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00179

Gnomad4 FIN exome AF: 0.00500

Gnomad4 NFE exome AF: 0.00711

Gnomad4 OTH exome AF: 0.00556

GnomAD4 genome AF: 0.00441 AC: 671 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.00392 AC XY: 292 AN XY: 74478

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.00682

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00565 Hom.: 0

Bravo AF: 0.00433

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	BORCS8-MEF2B: BP4, BP7; MEF2B: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Sep 07, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.9
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: rs151213204; hg19: chr19-19257933;