rs12091047

Variant names:

• chr1-19445431-C-T
• rs12091047
• NM_004930.5:c.4-25681G>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.4-25681G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,628 control chromosomes in the GnomAD database, including 7,684 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 (7684 hom., cov: 30)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 7 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]

ENSG00000306329 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 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.4-25681G>A		intron	N/A	NP_004921.1	A0A384MR50
	CAPZB	NM_001282162.2		c.91-25681G>A		intron	N/A	NP_001269091.1	B1AK88
	CAPZB	NM_001206540.3		c.4-25681G>A		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.4-25681G>A		intron	N/A	ENSP00000264202.7	P47756-2
	CAPZB	ENST00000375144.6	TSL:1	c.4-25681G>A		intron	N/A	ENSP00000364286.2	B1AK87
	CAPZB	ENST00000433834.5	TSL:2	c.91-25681G>A		intron	N/A	ENSP00000401010.1	B1AK88

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47005 AN: 151512 Hom.: 7668 Cov.: 30

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.310 AC: 47060 AN: 151628 Hom.: 7684 Cov.: 30 AF XY: 0.311 AC XY: 22997 AN XY: 74060

African (AFR) AF: 0.208 AC: 8604 AN: 41296

American (AMR) AF: 0.330 AC: 5035 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3466

East Asian (EAS) AF: 0.349 AC: 1797 AN: 5148

South Asian (SAS) AF: 0.362 AC: 1740 AN: 4800

European-Finnish (FIN) AF: 0.327 AC: 3420 AN: 10448

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 24067 AN: 67920

Other (OTH) AF: 0.323 AC: 680 AN: 2108

Alfa AF: 0.343 Hom.: 11635

Bravo AF: 0.307

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.42
PhyloP100		-0.050
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: rs12091047; hg19: chr1-19771925;