1-19423400-C-T

Variant names:

• chr1-19423400-C-T
• rs12033437
• NM_004930.5:c.4-3650G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004930.5(CAPZB):​c.4-3650G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,486 control chromosomes in the GnomAD database, including 7,571 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 0.31 (7571 hom., cov: 30)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPZB	NM_004930.5	c.4-3650G>A		intron_variant	Intron 1 of 8	ENST00000264202.8	NP_004921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPZB	ENST00000264202.8	c.4-3650G>A		intron_variant	Intron 1 of 8	1	NM_004930.5	ENSP00000264202.7

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47344 AN: 151368 Hom.: 7556 Cov.: 30

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.313 AC: 47400 AN: 151486 Hom.: 7571 Cov.: 30 AF XY: 0.311 AC XY: 23008 AN XY: 73944

African (AFR) AF: 0.249 AC: 10257 AN: 41262

American (AMR) AF: 0.324 AC: 4940 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1293 AN: 3466

East Asian (EAS) AF: 0.352 AC: 1806 AN: 5134

South Asian (SAS) AF: 0.316 AC: 1513 AN: 4790

European-Finnish (FIN) AF: 0.329 AC: 3418 AN: 10386

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23143 AN: 67908

Other (OTH) AF: 0.319 AC: 671 AN: 2106

Alfa AF: 0.333 Hom.: 6867

Bravo AF: 0.311

Asia WGS AF: 0.352 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.5
DANN	Benign	0.50
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12033437; hg19: chr1-19749894;