1-19428536-T-C

Position:

• chr1-19428536-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004930.5(CAPZB):​c.4-8786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,082 control chromosomes in the GnomAD database, including 21,614 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 0.53 (21614 hom., cov: 32)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZB	NM_004930.5	c.4-8786A>G		intron_variant		ENST00000264202.8	NP_004921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPZB	ENST00000264202.8	c.4-8786A>G		intron_variant		1	NM_004930.5	ENSP00000264202.7

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79947 AN: 151966 Hom.: 21579 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.525

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 80032 AN: 152082 Hom.: 21614 Cov.: 32 AF XY: 0.522 AC XY: 38811 AN XY: 74334

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.526

Alfa AF: 0.463 Hom.: 7977

Bravo AF: 0.541

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.30

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

LitVar

Other links and lift over

dbSNP: rs1472565; hg19: chr1-19755030; COSMIC: COSV51651854; COSMIC: COSV51651854;