rs3765069

Variant names:

• chr19-50433121-C-A
• rs3765069
• NM_004533.4:c.19+149C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50433121-C-A
• chr19-50433121-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004533.4(MYBPC2):​c.19+149C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000952 in 840,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000095 (0 hom.)
• Consequence: MYBPC2 NM_004533.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 10 publications found

Genes affected

MYBPC2 (HGNC:7550): (myosin binding protein C2) This gene encodes a member of the myosin-binding protein C family. This family includes the fast-, slow- and cardiac-type isoforms, each of which is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The protein encoded by this locus is referred to as the fast-type isoform. Mutations in the related but distinct genes encoding the slow-type and cardiac-type isoforms have been associated with distal arthrogryposis, type 1 and hypertrophic cardiomyopathy, respectively. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004533.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC2	NM_004533.4	MANE Select	c.19+149C>A		intron	N/A	NP_004524.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC2	ENST00000357701.6	TSL:1 MANE Select	c.19+149C>A		intron	N/A	ENSP00000350332.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000952 AC: 8 AN: 840076 Hom.: 0 AF XY: 0.00000954 AC XY: 4 AN XY: 419172

African (AFR) AF: 0.00 AC: 0 AN: 18402

American (AMR) AF: 0.00 AC: 0 AN: 16592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15428

East Asian (EAS) AF: 0.00 AC: 0 AN: 29098

South Asian (SAS) AF: 0.00 AC: 0 AN: 51272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3284

European-Non Finnish (NFE) AF: 0.0000126 AC: 8 AN: 637338

Other (OTH) AF: 0.00 AC: 0 AN: 38110

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.82
PhyloP100		-0.22
PromoterAI		0.011	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3765069; hg19: chr19-50936378;