dbSNP rs758187: MYOCD:c.-435T>C (chr17-12665754-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001146312.3(MYOCD):c.-435T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 158,126 control chromosomes in the GnomAD database, including 13,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 13574 hom., cov: 33)

Exomes 𝑓: 0.23 ( 196 hom. )

Consequence

MYOCD
NM_001146312.3 upstream_gene

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.664

Publications

1 publications found

Variant links:

Genes affected

MYOCD (HGNC:16067): (myocardin) This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

MYOCD Gene-Disease associations (from GenCC):

megabladder, congenital
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MYOCD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-12665754-T-C is Benign according to our data. Variant chr17-12665754-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253022.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOCD	NM_001146312.3 link	c.-435T>C		upstream_gene_variant		ENST00000425538.6	NP_001139784.1	Q8IZQ8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538.6 link	c.-435T>C		upstream_gene_variant		1	NM_001146312.3	ENSP00000401678.1		Q8IZQ8-3
MYOCD	ENST00000579237.5 link	n.-435T>C		upstream_gene_variant		4		ENSP00000462694.1		J3KSX3

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57738

AN:

152024

Hom.:

13526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.353

GnomAD4 exome

AF:

0.232

AC:

1391

AN:

5984

Hom.:

196

AF XY:

0.229

AC XY:

692

AN XY:

3020

show subpopulations

African (AFR)

AF:

0.629

AC:

156

AN:

248

American (AMR)

AF:

0.348

AC:

AN:

178

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

AN:

274

East Asian (EAS)

AF:

0.190

AC:

AN:

364

South Asian (SAS)

AF:

0.217

AC:

AN:

European-Finnish (FIN)

AF:

0.203

AC:

AN:

192

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.210

AC:

883

AN:

4206

Other (OTH)

AF:

0.231

AC:

AN:

390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.380

AC:

57847

AN:

152142

Hom.:

13574

Cov.:

AF XY:

0.378

AC XY:

28125

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.675

AC:

28008

AN:

41516

American (AMR)

AF:

0.359

AC:

5490

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

946

AN:

3468

East Asian (EAS)

AF:

0.250

AC:

1282

AN:

5132

South Asian (SAS)

AF:

0.210

AC:

1010

AN:

4820

European-Finnish (FIN)

AF:

0.294

AC:

3116

AN:

10604

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16963

AN:

67978

Other (OTH)

AF:

0.350

AC:

741

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1611

3223

4834

6446

8057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.317

Hom.:

1257

Bravo

AF:

0.403

Asia WGS

AF:

0.229

AC:

799

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 18028454) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.2

(source)

DANN

Benign

0.32

PhyloP100

-0.66

PromoterAI

0.025

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over