chr1-19428536-T-C

Variant names:

• chr1-19428536-T-C
• rs1472565
• NM_004930.5:c.4-8786A>G

Variant summary

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

The NM_004930.5(CAPZB):​c.4-8786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,082 control chromosomes in the GnomAD database, including 21,614 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 0.53 (21614 hom., cov: 32)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004930.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZB	NM_004930.5	MANE Select	c.4-8786A>G		intron	N/A	NP_004921.1	A0A384MR50
	CAPZB	NM_001282162.2		c.91-8786A>G		intron	N/A	NP_001269091.1	B1AK88
	CAPZB	NM_001206540.3		c.4-8786A>G		intron	N/A	NP_001193469.1	P47756-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZB	ENST00000264202.8	TSL:1 MANE Select	c.4-8786A>G		intron	N/A	ENSP00000264202.7	P47756-2
	CAPZB	ENST00000375144.6	TSL:1	c.4-8786A>G		intron	N/A	ENSP00000364286.2	B1AK87
	CAPZB	ENST00000433834.5	TSL:2	c.91-8786A>G		intron	N/A	ENSP00000401010.1	B1AK88

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79947 AN: 151966 Hom.: 21579 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.526 AC: 80032 AN: 152082 Hom.: 21614 Cov.: 32 AF XY: 0.522 AC XY: 38811 AN XY: 74334

African (AFR) AF: 0.645 AC: 26745 AN: 41458

American (AMR) AF: 0.563 AC: 8612 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3468

East Asian (EAS) AF: 0.494 AC: 2562 AN: 5188

South Asian (SAS) AF: 0.428 AC: 2067 AN: 4826

European-Finnish (FIN) AF: 0.432 AC: 4567 AN: 10570

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31935 AN: 67972

Other (OTH) AF: 0.526 AC: 1110 AN: 2110

Alfa AF: 0.467 Hom.: 9040

Bravo AF: 0.541

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.30
PhyloP100		-0.27
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: rs1472565; hg19: chr1-19755030; COSMIC: COSV51651854; COSMIC: COSV51651854;