rs73451796

chr11-47346416-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000256.3(MYBPC3):c.927-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000932 in 1,504,346 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (4 hom.)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.449

Genes affected

MYBPC3 (HGNC:7551): (myosin binding protein C3) MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. MYBPC3 is expressed exclusively in heart muscle and is a key regulator of cardiac contraction. Mutations in this gene are a frequent cause of familial hypertrophic cardiomyopathy. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-47346416-C-G is Benign according to our data. Variant chr11-47346416-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1189061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0047 (716/152266) while in subpopulation AFR AF= 0.0164 (681/41546). AF 95% confidence interval is 0.0154. There are 8 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC3	NM_000256.3	c.927-46G>C		intron_variant		ENST00000545968.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC3	ENST00000545968.6	c.927-46G>C		intron_variant		5	NM_000256.3	P4
MYBPC3	ENST00000399249.6	c.927-46G>C		intron_variant		5		A2
MYBPC3	ENST00000544791.1	c.927-46G>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00469 AC: 714 AN: 152148 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00147 AC: 191 AN: 130238 Hom.: 2 AF XY: 0.00106 AC XY: 71 AN XY: 66954

Gnomad AFR exome AF: 0.0184

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000380

Gnomad OTH exome AF: 0.000283

GnomAD4 exome AF: 0.000507 AC: 686 AN: 1352080 Hom.: 4 Cov.: 32 AF XY: 0.000454 AC XY: 300 AN XY: 660132

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000281

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000142

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00470 AC: 716 AN: 152266 Hom.: 8 Cov.: 32 AF XY: 0.00465 AC XY: 346 AN XY: 74444

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00326 Hom.: 0

Bravo AF: 0.00544

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	2.5
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs73451796; hg19: chr11-47367967;