chr11-47349933-AG-A

Variant names:

• chr11-47349933-AG-A
• rs11570050
• NM_000256.3:c.506-12delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000256.3(MYBPC3):​c.506-12delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). The gene MYBPC3 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.61 (30296 hom., cov: 0)
  • Exomes 𝑓: 0.70 (352985 hom.)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:18
• Conservation: PhyloP100: 0.0850
• Publications: 11 publications found

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]

MYBPC3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 4

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• left ventricular noncompaction 10

  Inheritance: AD, AR Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• atrial fibrillation

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Specifications for MYBPC3 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-47349933-AG-A is Benign according to our data. Variant chr11-47349933-AG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 42763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC3	NM_000256.3	MANE Select	c.506-12delC		intron	N/A	NP_000247.2	Q14896-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC3	ENST00000545968.6	TSL:5 MANE Select	c.506-12delC		intron	N/A	ENSP00000442795.1	Q14896-1
	MYBPC3	ENST00000399249.6	TSL:5	c.506-12delC		intron	N/A	ENSP00000382193.2	A8MXZ9
	MYBPC3	ENST00000544791.1	TSL:5	n.506-12delC		intron	N/A	ENSP00000444259.1	F5GZR4

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93300 AN: 151942 Hom.: 30276 Cov.: 0

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.678

GnomAD2 exomes AF: 0.665 AC: 135009 AN: 202962 AF XY: 0.676

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.596

Gnomad ASJ exome AF: 0.727

Gnomad EAS exome AF: 0.628

Gnomad FIN exome AF: 0.616

Gnomad NFE exome AF: 0.717

Gnomad OTH exome AF: 0.716

GnomAD4 exome AF: 0.698 AC: 1001523 AN: 1434702 Hom.: 352985 Cov.: 0 AF XY: 0.700 AC XY: 497885 AN XY: 711092

African (AFR) AF: 0.383 AC: 12604 AN: 32910

American (AMR) AF: 0.603 AC: 24538 AN: 40662

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 18553 AN: 25584

East Asian (EAS) AF: 0.577 AC: 22066 AN: 38222

South Asian (SAS) AF: 0.709 AC: 58419 AN: 82350

European-Finnish (FIN) AF: 0.622 AC: 31909 AN: 51288

Middle Eastern (MID) AF: 0.728 AC: 4121 AN: 5658

European-Non Finnish (NFE) AF: 0.717 AC: 787620 AN: 1098642

Other (OTH) AF: 0.702 AC: 41693 AN: 59386

GnomAD4 genome AF: 0.614 AC: 93369 AN: 152060 Hom.: 30296 Cov.: 0 AF XY: 0.612 AC XY: 45467 AN XY: 74324

African (AFR) AF: 0.390 AC: 16192 AN: 41472

American (AMR) AF: 0.660 AC: 10094 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2502 AN: 3472

East Asian (EAS) AF: 0.647 AC: 3335 AN: 5152

South Asian (SAS) AF: 0.728 AC: 3516 AN: 4828

European-Finnish (FIN) AF: 0.604 AC: 6374 AN: 10548

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48921 AN: 67974

Other (OTH) AF: 0.682 AC: 1442 AN: 2114

Alfa AF: 0.687 Hom.: 6634

Bravo AF: 0.607

Asia WGS AF: 0.709 AC: 2467 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	4	Hypertrophic cardiomyopathy 4 (4)
-	-	2	Cardiomyopathy (2)
-	-	2	Hypertrophic cardiomyopathy (2)
-	-	2	not provided (2)
-	-	1	Left ventricular noncompaction 10 (1)
-	-	1	Left ventricular noncompaction cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.085
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: rs11570050; hg19: chr11-47371484;