rs214305

Positions:

• chr1-19363563-G-A
• chr1-19363563-G-C

Variant summary

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

The NM_004930.5(CAPZB):​c.330-6000C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,952 control chromosomes in the GnomAD database, including 9,285 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 0.33 (9285 hom., cov: 31)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPZB	NM_004930.5	c.330-6000C>T		intron_variant		ENST00000264202.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPZB	ENST00000264202.8	c.330-6000C>T		intron_variant		1	NM_004930.5	P3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50538 AN: 151834 Hom.: 9284 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.333 AC: 50545 AN: 151952 Hom.: 9285 Cov.: 31 AF XY: 0.339 AC XY: 25200 AN XY: 74250

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.361

Alfa AF: 0.225 Hom.: 558

Bravo AF: 0.328

Asia WGS AF: 0.457 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs214305; hg19: chr1-19690057;