rs1405712

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-101594747-C-T
• chr12-101594747-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000550514.5(MYBPC1):​c.-195+26242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 245,714 control chromosomes in the GnomAD database, including 17,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9846 hom., cov: 32)
  • Exomes 𝑓: 0.39 (7449 hom.)
• Consequence: MYBPC1 ENST00000550514.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 12-101594747-C-T is Benign according to our data. Variant chr12-101594747-C-T is described in ClinVar as Benign. ClinVar VariationId is 1296793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

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>T		upstream_gene	N/A	NP_002456.2
	MYBPC1	NM_001404675.1		c.-324C>T		upstream_gene	N/A	NP_001391604.1
	MYBPC1	NM_001254718.3		c.-324C>T		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>T		intron	N/A	ENSP00000447404.1	F8W1Z9
	MYBPC1	ENST00000361466.7	TSL:1 MANE Select	c.-324C>T		upstream_gene	N/A	ENSP00000354849.2	Q00872-4
	MYBPC1	ENST00000361685.6	TSL:1	c.-324C>T		upstream_gene	N/A	ENSP00000354845.2	Q00872-2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53828 AN: 151738 Hom.: 9851 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.390 AC: 36599 AN: 93856 Hom.: 7449 AF XY: 0.391 AC XY: 18647 AN XY: 47750

African (AFR) AF: 0.247 AC: 927 AN: 3756

American (AMR) AF: 0.342 AC: 1423 AN: 4158

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1772 AN: 3924

East Asian (EAS) AF: 0.476 AC: 3893 AN: 8186

South Asian (SAS) AF: 0.387 AC: 898 AN: 2320

European-Finnish (FIN) AF: 0.391 AC: 1927 AN: 4926

Middle Eastern (MID) AF: 0.440 AC: 212 AN: 482

European-Non Finnish (NFE) AF: 0.386 AC: 23066 AN: 59748

Other (OTH) AF: 0.390 AC: 2481 AN: 6356

GnomAD4 genome AF: 0.355 AC: 53845 AN: 151858 Hom.: 9846 Cov.: 32 AF XY: 0.356 AC XY: 26438 AN XY: 74174

African (AFR) AF: 0.257 AC: 10642 AN: 41400

American (AMR) AF: 0.345 AC: 5255 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1545 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2553 AN: 5178

South Asian (SAS) AF: 0.390 AC: 1872 AN: 4804

European-Finnish (FIN) AF: 0.405 AC: 4262 AN: 10518

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26594 AN: 67938

Other (OTH) AF: 0.391 AC: 821 AN: 2102

Alfa AF: 0.377 Hom.: 23640

Bravo AF: 0.347

Asia WGS AF: 0.424 AC: 1474 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.75
PhyloP100		0.036
PromoterAI		0.011	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;