rs2052003

Positions:

• chr17-12683015-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.55+16772C>A		intron_variant		ENST00000425538.6
MYOCD-AS1	NR_104605.1	n.814-10824G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.55+16772C>A		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.55+16772C>A		intron_variant		1		A2
MYOCD-AS1	ENST00000445508.1	n.814-10824G>T		intron_variant, non_coding_transcript_variant		1
MYOCD	ENST00000579237.5	c.55+16772C>A		intron_variant, NMD_transcript_variant		4

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

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.361

Alfa AF: 0.304 Hom.: 15074

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

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: rs2052003; hg19: chr17-12586332;