chr1-19356807-G-T

Variant names:

• chr1-19356807-G-T
• rs169957
• NM_004930.5:c.472-56C>A

Variant summary

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

The NM_004930.5(CAPZB):​c.472-56C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,145,724 control chromosomes in the GnomAD database, including 105,759 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 0.45 (15900 hom., cov: 31)
  • Exomes 𝑓: 0.43 (89859 hom.)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPZB	NM_004930.5	c.472-56C>A		intron_variant	Intron 5 of 8	ENST00000264202.8	NP_004921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPZB	ENST00000264202.8	c.472-56C>A		intron_variant	Intron 5 of 8	1	NM_004930.5	ENSP00000264202.7

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68848 AN: 151778 Hom.: 15870 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.425 AC: 422391 AN: 993828 Hom.: 89859 AF XY: 0.422 AC XY: 214876 AN XY: 509546

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.454 AC: 68933 AN: 151896 Hom.: 15900 Cov.: 31 AF XY: 0.457 AC XY: 33947 AN XY: 74228

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.452

Alfa AF: 0.420 Hom.: 22803

Bravo AF: 0.462

Asia WGS AF: 0.483 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.046
DANN	Benign	0.60

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: rs169957; hg19: chr1-19683301;