17-12760404-G-T

Position:

• chr17-12760404-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146312.3(MYOCD):​c.2332-246G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 469,814 control chromosomes in the GnomAD database, including 20,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5351 hom., cov: 33)
  • Exomes 𝑓: 0.30 (14818 hom.)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0340

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]

ARHGAP44-AS1 (HGNC:55326): (ARHGAP44 and MYOCD antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-12760404-G-T is Benign according to our data. Variant chr17-12760404-G-T is described in ClinVar as [Benign]. Clinvar id is 1277125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.2332-246G>T		intron_variant		ENST00000425538.6
ARHGAP44-AS1	NR_104607.1	n.3457C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.2332-246G>T		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.2188-246G>T		intron_variant		1		A2
MYOCD	ENST00000443061.1	c.1318-246G>T		intron_variant		1
ARHGAP44-AS1	ENST00000584772.1	n.3415C>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36259 AN: 152020 Hom.: 5351 Cov.: 33

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.296 AC: 94003 AN: 317676 Hom.: 14818 Cov.: 2 AF XY: 0.293 AC XY: 48971 AN XY: 167008

Gnomad4 AFR exome AF: 0.0738

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.238 AC: 36255 AN: 152138 Hom.: 5351 Cov.: 33 AF XY: 0.241 AC XY: 17930 AN XY: 74380

Gnomad4 AFR AF: 0.0730

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.246

Alfa AF: 0.131 Hom.: 287

Bravo AF: 0.219

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
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: rs28730827; hg19: chr17-12663721;