ENST00000550514.5:c.-195+26242C>G

Variant names:

• chr12-101594747-C-G
• rs1405712
• ENST00000550514.5:c.-195+26242C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The ENST00000550514.5(MYBPC1):​c.-195+26242C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 246,240 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: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: MYBPC1 ENST00000550514.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 7 publications found

Genes affected

MYBPC1 (HGNC:7549): (myosin binding protein C1) This gene encodes a member of the myosin-binding protein C family. Myosin-binding protein C family members are myosin-associated proteins found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The encoded protein is the slow skeletal muscle isoform of myosin-binding protein C and plays an important role in muscle contraction by recruiting muscle-type creatine kinase to myosin filaments. Mutations in this gene are associated with distal arthrogryposis type I. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

MYBPC1 Gene-Disease associations (from GenCC):

• arthrogryposis, distal, type 1B

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• myopathy, congenital, with tremor

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• lethal congenital contracture syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• lethal congenital contracture syndrome 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000244 (37/151934) while in subpopulation AFR AF = 0.000797 (33/41418). AF 95% confidence interval is 0.000583. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550514.5. 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
	MYBPC1	NM_002465.4	MANE Select	c.-324C>G		upstream_gene	N/A	NP_002456.2
	MYBPC1	NM_001404675.1		c.-324C>G		upstream_gene	N/A	NP_001391604.1
	MYBPC1	NM_001254718.3		c.-324C>G		upstream_gene	N/A	NP_001241647.1	Q00872-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC1	ENST00000550514.5	TSL:5	c.-195+26242C>G		intron	N/A	ENSP00000447404.1	F8W1Z9
	MYBPC1	ENST00000361466.7	TSL:1 MANE Select	c.-324C>G		upstream_gene	N/A	ENSP00000354849.2	Q00872-4
	MYBPC1	ENST00000361685.6	TSL:1	c.-324C>G		upstream_gene	N/A	ENSP00000354845.2	Q00872-2

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 151814 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000775

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000636 AC: 6 AN: 94306 Hom.: 0 AF XY: 0.0000208 AC XY: 1 AN XY: 47998

African (AFR) AF: 0.00159 AC: 6 AN: 3764

American (AMR) AF: 0.00 AC: 0 AN: 4166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3950

East Asian (EAS) AF: 0.00 AC: 0 AN: 8220

South Asian (SAS) AF: 0.00 AC: 0 AN: 2334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 486

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60044

Other (OTH) AF: 0.00 AC: 0 AN: 6388

GnomAD4 genome AF: 0.000244 AC: 37 AN: 151934 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 74218

African (AFR) AF: 0.000797 AC: 33 AN: 41418

American (AMR) AF: 0.000262 AC: 4 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 23640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		0.036
PromoterAI		0.015	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1405712; hg19: chr12-101988525;