chr12-101653096-AC-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002465.4(MYBPC1):c.1634-18delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,610,676 control chromosomes in the GnomAD database, including 57,525 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3990 hom., cov: 25)

Exomes 𝑓: 0.27 ( 53535 hom. )

Consequence

MYBPC1
NM_002465.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.895

Publications

3 publications found

Variant links:

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

MYBPC1 links:

ENSG00000257514 (HGNC:):

ENSG00000257514 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP6

Variant 12-101653096-AC-A is Benign according to our data. Variant chr12-101653096-AC-A is described in ClinVar as Benign. ClinVar VariationId is 258658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002465.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYBPC1	NM_002465.4	MANE Select	c.1634-18delC	intron	N/A	NP_002456.2
MYBPC1	NM_001404675.1		c.1634-18delC	intron	N/A	NP_001391604.1
MYBPC1	NM_001254718.3		c.1559-18delC	intron	N/A	NP_001241647.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYBPC1	ENST00000361466.7	TSL:1 MANE Select	c.1634-18delC	intron	N/A	ENSP00000354849.2
MYBPC1	ENST00000361685.6	TSL:1	c.1634-18delC	intron	N/A	ENSP00000354845.2
MYBPC1	ENST00000545503.6	TSL:1	c.1559-18delC	intron	N/A	ENSP00000440034.2

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33631

AN:

151974

Hom.:

3992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.224

AC:

56156

AN:

250220

AF XY:

0.231

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.0792

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.265

AC:

386654

AN:

1458584

Hom.:

53535

Cov.:

AF XY:

0.265

AC XY:

192262

AN XY:

725802

show subpopulations

African (AFR)

AF:

0.143

AC:

4793

AN:

33450

American (AMR)

AF:

0.144

AC:

6458

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

7868

AN:

26116

East Asian (EAS)

AF:

0.0890

AC:

3533

AN:

39688

South Asian (SAS)

AF:

0.229

AC:

19768

AN:

86208

European-Finnish (FIN)

AF:

0.240

AC:

12614

AN:

52598

Middle Eastern (MID)

AF:

0.321

AC:

1847

AN:

5762

European-Non Finnish (NFE)

AF:

0.283

AC:

314176

AN:

1109764

Other (OTH)

AF:

0.259

AC:

15597

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

13067

26135

39202

52270

65337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10304

20608

30912

41216

51520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.221

AC:

33627

AN:

152092

Hom.:

3990

Cov.:

AF XY:

0.217

AC XY:

16157

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.144

AC:

5962

AN:

41502

American (AMR)

AF:

0.189

AC:

2896

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1059

AN:

3470

East Asian (EAS)

AF:

0.101

AC:

522

AN:

5176

South Asian (SAS)

AF:

0.223

AC:

1075

AN:

4818

European-Finnish (FIN)

AF:

0.232

AC:

2454

AN:

10566

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18899

AN:

67952

Other (OTH)

AF:

0.229

AC:

484

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1328

2657

3985

5314

6642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.190

Hom.:

620

Bravo

AF:

0.211

Asia WGS

AF:

0.155

AC:

541

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Myopathy, congenital, with tremor

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Lethal congenital contracture syndrome 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Jul 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arthrogryposis, distal, type 1B

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over