Genetic Variant MYBPC2:c.19+149C>T (chr19-50433121-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004533.4(MYBPC2):c.19+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 989,436 control chromosomes in the GnomAD database, including 84,795 homozygotes. 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 0.37 ( 11510 hom., cov: 31)

Exomes 𝑓: 0.41 ( 73285 hom. )

Consequence

MYBPC2
NM_004533.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.218

Publications

10 publications found

Variant links:

Genes affected

MYBPC2 (HGNC:7550): (myosin binding protein C2) This gene encodes a member of the myosin-binding protein C family. This family includes the fast-, slow- and cardiac-type isoforms, each of which is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The protein encoded by this locus is referred to as the fast-type isoform. Mutations in the related but distinct genes encoding the slow-type and cardiac-type isoforms have been associated with distal arthrogryposis, type 1 and hypertrophic cardiomyopathy, respectively. [provided by RefSeq, Jul 2012]

MYBPC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004533.4. 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
	MYBPC2	NM_004533.4	MANE Select	c.19+149C>T		intron	N/A	NP_004524.3	A0A140VJQ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYBPC2	ENST00000357701.6	TSL:1 MANE Select	c.19+149C>T	intron	N/A	ENSP00000350332.4	Q14324
MYBPC2	ENST00000966357.1		c.19+149C>T	intron	N/A	ENSP00000636416.1
MYBPC2	ENST00000966353.1		c.19+149C>T	intron	N/A	ENSP00000636412.1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56100

AN:

151818

Hom.:

11498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.452

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.435

GnomAD4 exome

AF:

0.408

AC:

341420

AN:

837500

Hom.:

73285

AF XY:

0.412

AC XY:

171976

AN XY:

417864

show subpopulations

African (AFR)

AF:

0.177

AC:

3246

AN:

18370

American (AMR)

AF:

0.527

AC:

8729

AN:

16562

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

7699

AN:

15408

East Asian (EAS)

AF:

0.482

AC:

14004

AN:

29026

South Asian (SAS)

AF:

0.515

AC:

26345

AN:

51146

European-Finnish (FIN)

AF:

0.411

AC:

12544

AN:

30496

Middle Eastern (MID)

AF:

0.536

AC:

1757

AN:

3276

European-Non Finnish (NFE)

AF:

0.396

AC:

251287

AN:

635200

Other (OTH)

AF:

0.416

AC:

15809

AN:

38016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9403

18807

28210

37614

47017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6668

13336

20004

26672

33340

<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:

0.369

AC:

56127

AN:

151936

Hom.:

11510

Cov.:

AF XY:

0.375

AC XY:

27854

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.191

AC:

7925

AN:

41438

American (AMR)

AF:

0.490

AC:

7482

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

1732

AN:

3472

East Asian (EAS)

AF:

0.522

AC:

2682

AN:

5140

South Asian (SAS)

AF:

0.520

AC:

2503

AN:

4818

European-Finnish (FIN)

AF:

0.415

AC:

4390

AN:

10570

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27934

AN:

67900

Other (OTH)

AF:

0.436

AC:

920

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1704

3407

5111

6814

8518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.259

Hom.:

711

Bravo

AF:

0.368

Asia WGS

AF:

0.519

AC:

1805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.2

(source)

DANN

Benign

0.87

PhyloP100

-0.22

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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