Variant chr19-19145764-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145785.2(MEF2B):c.*33C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,555,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

MEF2B
NM_001145785.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Variant links:

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]

MEF2B links:

BORCS8-MEF2B (HGNC:):

BORCS8-MEF2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03958237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2B	NM_001145785.2 linkuse as main transcript	c.*33C>T		3_prime_UTR_variant	9/9	ENST00000424583.7
BORCS8-MEF2B	NR_027308.2 linkuse as main transcript	n.1494C>T		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2B	ENST00000424583.7 linkuse as main transcript	c.*33C>T		3_prime_UTR_variant	9/9	5	NM_001145785.2	P4	Q02080-2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000154

AC:

AN:

149034

Hom.:

AF XY:

0.000174

AC XY:

AN XY:

80268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00117

Gnomad NFE exome

AF:

0.0000928

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000181

AC:

254

AN:

1403080

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

121

AN XY:

692358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.000258

GnomAD4 genome

AF:

0.000177

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000156

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.1028C>T (p.S343L) alteration is located in exon 10 (coding exon 7) of the BORCS8-MEF2B gene. This alteration results from a C to T substitution at nucleotide position 1028, causing the serine (S) at amino acid position 343 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.18

DANN

Benign

0.90

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.38

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-0.65

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

-0.79

N;.

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.17

T;T

Vest4

0.12

MVP

0.11

MPC

0.33

ClinPred

0.040

GERP RS

-3.6

gMVP

0.036

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over