chr17-12683015-C-A

Variant names:

• chr17-12683015-C-A
• rs2052003
• NM_001146312.3:c.55+16772C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146312.3(MYOCD):​c.55+16772C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,032 control chromosomes in the GnomAD database, including 13,292 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 0.39 (13292 hom., cov: 32)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 10 publications found

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-AS1 (HGNC:40750): (MYOCD antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.55+16772C>A		intron_variant	Intron 1 of 13	ENST00000425538.6	NP_001139784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538.6	c.55+16772C>A		intron_variant	Intron 1 of 13	1	NM_001146312.3	ENSP00000401678.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59111 AN: 151912 Hom.: 13250 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.363

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59211 AN: 152032 Hom.: 13292 Cov.: 32 AF XY: 0.385 AC XY: 28621 AN XY: 74320

African (AFR) AF: 0.629 AC: 26067 AN: 41464

American (AMR) AF: 0.375 AC: 5740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3466

East Asian (EAS) AF: 0.252 AC: 1297 AN: 5156

South Asian (SAS) AF: 0.228 AC: 1097 AN: 4816

European-Finnish (FIN) AF: 0.287 AC: 3028 AN: 10566

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19825 AN: 67962

Other (OTH) AF: 0.361 AC: 762 AN: 2112

Alfa AF: 0.326 Hom.: 28424

Bravo AF: 0.411

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.44
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs2052003; hg19: chr17-12586332;