chr12-101595058-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_002465.4(MYBPC1):c.-13T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,612,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

MYBPC1
NM_002465.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.226

Publications

1 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: 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

MYBPC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-101595058-T-C is Benign according to our data. Variant chr12-101595058-T-C is described in ClinVar as Benign. ClinVar VariationId is 306706.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000736 (112/152234) while in subpopulation AFR AF = 0.00262 (109/41552). AF 95% confidence interval is 0.00222. There are 0 homozygotes in GnomAd4. There are 53 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: 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	UniProt
MYBPC1	NM_002465.4	MANE Select	c.-13T>C	5_prime_UTR	Exon 1 of 32	NP_002456.2
MYBPC1	NM_001404675.1		c.-13T>C	5_prime_UTR	Exon 1 of 30	NP_001391604.1
MYBPC1	NM_001254718.3		c.-13T>C	5_prime_UTR	Exon 1 of 30	NP_001241647.1	Q00872-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYBPC1	ENST00000361466.7	TSL:1 MANE Select	c.-13T>C	5_prime_UTR	Exon 1 of 32	ENSP00000354849.2	Q00872-4
MYBPC1	ENST00000361685.6	TSL:1	c.-13T>C	5_prime_UTR	Exon 1 of 31	ENSP00000354845.2	Q00872-2
MYBPC1	ENST00000545503.6	TSL:1	c.-13T>C	5_prime_UTR	Exon 1 of 30	ENSP00000440034.2	Q00872-10

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000958

GnomAD2 exomes

AF:

0.000207

AC:

AN:

251054

AF XY:

0.000184

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1460668

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726670

show subpopulations

African (AFR)

AF:

0.00245

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111044

Other (OTH)

AF:

0.0000828

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000736

AC:

112

AN:

152234

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00262

AC:

109

AN:

41552

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000128

Hom.:

Bravo

AF:

0.000710

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Arthrogryposis, distal, type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.6

(source)

DANN

Benign

0.64

PhyloP100

-0.23

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=299/1

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over