rs12045440

chr1-19439024-T-G

Variant summary

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

The NM_004930.5(CAPZB):c.4-19274A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,160 control chromosomes in the GnomAD database, including 7,389 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 0.30 (7389 hom., cov: 33)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPZB	NM_004930.5	c.4-19274A>C		intron_variant		ENST00000264202.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPZB	ENST00000264202.8	c.4-19274A>C		intron_variant		1	NM_004930.5	P3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46154 AN: 152042 Hom.: 7372 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.304 AC: 46209 AN: 152160 Hom.: 7389 Cov.: 33 AF XY: 0.303 AC XY: 22539 AN XY: 74384

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.313

Alfa AF: 0.343 Hom.: 11561

Bravo AF: 0.301

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	11
Dann	Benign	0.66

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: rs12045440; hg19: chr1-19765518;