NM_002465.4:c.1196+285C>G

Variant names:

• chr12-101648435-C-G
• rs11110912
• NM_002465.4:c.1196+285C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002465.4(MYBPC1):​c.1196+285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,116 control chromosomes in the GnomAD database, including 1,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1743 hom., cov: 32)
• Consequence: MYBPC1 NM_002465.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82
• Publications: 9 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• digitotalar dysmorphism

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000257514 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-101648435-C-G is Benign according to our data. Variant chr12-101648435-C-G is described in ClinVar as Benign. ClinVar VariationId is 1238195.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC1	NM_002465.4	c.1196+285C>G		intron_variant	Intron 14 of 31	ENST00000361466.7	NP_002456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7	c.1196+285C>G		intron_variant	Intron 14 of 31	1	NM_002465.4	ENSP00000354849.2
MYBPC1	ENST00000551300.5	c.824+285C>G		intron_variant	Intron 15 of 31	1		ENSP00000447116.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21370 AN: 151998 Hom.: 1743 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21372 AN: 152116 Hom.: 1743 Cov.: 32 AF XY: 0.137 AC XY: 10206 AN XY: 74354

African (AFR) AF: 0.0698 AC: 2899 AN: 41518

American (AMR) AF: 0.132 AC: 2017 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3464

East Asian (EAS) AF: 0.101 AC: 523 AN: 5172

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4820

European-Finnish (FIN) AF: 0.0969 AC: 1025 AN: 10582

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12356 AN: 67958

Other (OTH) AF: 0.159 AC: 336 AN: 2116

Alfa AF: 0.161 Hom.: 306

Bravo AF: 0.137

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 30, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.065
DANN	Benign	0.29
PhyloP100		-1.8
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: rs11110912; hg19: chr12-102042213;