Genetic Variant CAPZB:c.472-56C>A (chr1-19356807-G-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_004930.5(CAPZB):c.472-56C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,145,724 control chromosomes in the GnomAD database, including 105,759 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 0.45 ( 15900 hom., cov: 31)

Exomes 𝑓: 0.43 ( 89859 hom. )

Consequence

CAPZB
NM_004930.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.551

Publications

11 publications found

Variant links:

Genes affected

CAPZB (HGNC:1491): (capping actin protein of muscle Z-line subunit beta) This gene encodes the beta subunit of the barbed-end actin binding protein, which belongs to the F-actin capping protein family. The capping protein is a heterodimeric actin capping protein that blocks actin filament assembly and disassembly at the fast growing (barbed) filament ends and functions in regulating actin filament dynamics as well as in stabilizing actin filament lengths in muscle and nonmuscle cells. A pseudogene of this gene is located on the long arm of chromosome 2. Multiple alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, Aug 2013]

CAPZB 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004930.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAPZB	NM_004930.5	MANE Select	c.472-56C>A	intron	N/A	NP_004921.1	A0A384MR50
CAPZB	NM_001282162.2		c.559-56C>A	intron	N/A	NP_001269091.1	B1AK88
CAPZB	NM_001206540.3		c.472-56C>A	intron	N/A	NP_001193469.1	P47756-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAPZB	ENST00000264202.8	TSL:1 MANE Select	c.472-56C>A	intron	N/A	ENSP00000264202.7	P47756-2
CAPZB	ENST00000375144.6	TSL:1	c.472-56C>A	intron	N/A	ENSP00000364286.2	B1AK87
CAPZB	ENST00000433834.5	TSL:2	c.559-56C>A	intron	N/A	ENSP00000401010.1	B1AK88

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68848

AN:

151778

Hom.:

15870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.451

GnomAD4 exome

AF:

0.425

AC:

422391

AN:

993828

Hom.:

89859

AF XY:

0.422

AC XY:

214876

AN XY:

509546

show subpopulations

African (AFR)

AF:

0.516

AC:

12516

AN:

24250

American (AMR)

AF:

0.522

AC:

21271

AN:

40776

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

9214

AN:

21448

East Asian (EAS)

AF:

0.602

AC:

22456

AN:

37292

South Asian (SAS)

AF:

0.375

AC:

27589

AN:

73610

European-Finnish (FIN)

AF:

0.429

AC:

21441

AN:

49944

Middle Eastern (MID)

AF:

0.416

AC:

1964

AN:

4724

European-Non Finnish (NFE)

AF:

0.411

AC:

286784

AN:

697234

Other (OTH)

AF:

0.430

AC:

19156

AN:

44550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12887

25774

38661

51548

64435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7412

14824

22236

29648

37060

<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:

0.454

AC:

68933

AN:

151896

Hom.:

15900

Cov.:

AF XY:

0.457

AC XY:

33947

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.510

AC:

21096

AN:

41392

American (AMR)

AF:

0.511

AC:

7804

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1453

AN:

3468

East Asian (EAS)

AF:

0.558

AC:

2884

AN:

5172

South Asian (SAS)

AF:

0.389

AC:

1875

AN:

4814

European-Finnish (FIN)

AF:

0.428

AC:

4510

AN:

10542

Middle Eastern (MID)

AF:

0.397

AC:

116

AN:

292

European-Non Finnish (NFE)

AF:

0.410

AC:

27835

AN:

67930

Other (OTH)

AF:

0.452

AC:

953

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1925

3850

5774

7699

9624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.423

Hom.:

34025

Bravo

AF:

0.462

Asia WGS

AF:

0.483

AC:

1675

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.046

(source)

DANN

Benign

0.60

PhyloP100

-0.55

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

Computational scores

Splicing

Publications

Other links and lift over