chr17-12760379-G-A

Position:

• chr17-12760379-G-A

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.2332-271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 420,866 control chromosomes in the GnomAD database, including 31,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (9047 hom., cov: 33)
  • Exomes 𝑓: 0.39 (22101 hom.)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.402

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 17-12760379-G-A is Benign according to our data. Variant chr17-12760379-G-A is described in ClinVar as [Benign]. Clinvar id is 1272626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.2332-271G>A		intron_variant		ENST00000425538.6
ARHGAP44-AS1	NR_104607.1	n.3482C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.2332-271G>A		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.2188-271G>A		intron_variant		1		A2
MYOCD	ENST00000443061.1	c.1318-271G>A		intron_variant		1
ARHGAP44-AS1	ENST00000584772.1	n.3440C>T		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47512 AN: 152048 Hom.: 9046 Cov.: 33

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.394 AC: 105738 AN: 268700 Hom.: 22101 Cov.: 0 AF XY: 0.396 AC XY: 56077 AN XY: 141468

Gnomad4 AFR exome AF: 0.0910

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.312 AC: 47510 AN: 152166 Hom.: 9047 Cov.: 33 AF XY: 0.318 AC XY: 23674 AN XY: 74386

Gnomad4 AFR AF: 0.0893

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.336

Alfa AF: 0.347 Hom.: 1237

Bravo AF: 0.296

Asia WGS AF: 0.466 AC: 1622 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.54

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: rs56138813; hg19: chr17-12663696;