rs7667

Positions:

• chr1-19392330-G-A

Variant summary

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

The NM_004930.5(CAPZB):​c.94-6704C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,588 control chromosomes in the GnomAD database, including 7,945 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 0.32 (7945 hom., cov: 28)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZB	NM_004930.5	c.94-6704C>T		intron_variant		ENST00000264202.8	NP_004921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPZB	ENST00000264202.8	c.94-6704C>T		intron_variant		1	NM_004930.5	ENSP00000264202	P3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48828 AN: 151468 Hom.: 7935 Cov.: 28

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.322 AC: 48861 AN: 151588 Hom.: 7945 Cov.: 28 AF XY: 0.320 AC XY: 23720 AN XY: 74050

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.318

Alfa AF: 0.340 Hom.: 7756

Bravo AF: 0.324

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.71

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: rs7667; hg19: chr1-19718824;