Variant 1-19419657-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004930.5(CAPZB):c.93+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,565,588 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 39 hom. )

Consequence

CAPZB
NM_004930.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.00008451

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.849

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-19419657-G-A is Benign according to our data. Variant chr1-19419657-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638432.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-19419657-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00438 (6196/1413250) while in subpopulation MID AF= 0.0233 (133/5700). AF 95% confidence interval is 0.0201. There are 39 homozygotes in gnomad4_exome. There are 3250 alleles in male gnomad4_exome subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High AC in GnomAd4 at 575 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPZB	NM_004930.5 linkuse as main transcript	c.93+4C>T		splice_donor_region_variant, intron_variant		ENST00000264202.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPZB	ENST00000264202.8 linkuse as main transcript	c.93+4C>T		splice_donor_region_variant, intron_variant		1	NM_004930.5	P3	P47756-2

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

576

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00530

AC:

1109

AN:

209130

Hom.:

AF XY:

0.00565

AC XY:

638

AN XY:

112878

show subpopulations

Gnomad AFR exome

AF:

0.000507

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.0310

Gnomad EAS exome

AF:

0.0000655

Gnomad SAS exome

AF:

0.00925

Gnomad FIN exome

AF:

0.00237

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.00673

GnomAD4 exome

AF:

0.00438

AC:

6196

AN:

1413250

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

3250

AN XY:

702162

show subpopulations

Gnomad4 AFR exome

AF:

0.000745

Gnomad4 AMR exome

AF:

0.00312

Gnomad4 ASJ exome

AF:

0.0302

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00851

Gnomad4 FIN exome

AF:

0.00201

Gnomad4 NFE exome

AF:

0.00369

Gnomad4 OTH exome

AF:

0.00619

GnomAD4 genome

AF:

0.00377

AC:

575

AN:

152338

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00456

Hom.:

Bravo

AF:

0.00391

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

CAPZB: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0030

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

dbscSNV1_RF

Benign

0.010

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over