NM_004930.5:c.4-19274A>C

Variant names:

• chr1-19439024-T-G
• rs12045440
• NM_004930.5:c.4-19274A>C

Variant summary

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

The NM_004930.5(CAPZB):​c.4-19274A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,160 control chromosomes in the GnomAD database, including 7,389 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 0.30 (7389 hom., cov: 33)
• Consequence: CAPZB NM_004930.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967
• Publications: 23 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 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.4-19274A>C		intron	N/A	NP_004921.1	A0A384MR50
	CAPZB	NM_001282162.2		c.91-19274A>C		intron	N/A	NP_001269091.1	B1AK88
	CAPZB	NM_001206540.3		c.4-19274A>C		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.4-19274A>C		intron	N/A	ENSP00000264202.7	P47756-2
	CAPZB	ENST00000375144.6	TSL:1	c.4-19274A>C		intron	N/A	ENSP00000364286.2	B1AK87
	CAPZB	ENST00000433834.5	TSL:2	c.91-19274A>C		intron	N/A	ENSP00000401010.1	B1AK88

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46154 AN: 152042 Hom.: 7372 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.304 AC: 46209 AN: 152160 Hom.: 7389 Cov.: 33 AF XY: 0.303 AC XY: 22539 AN XY: 74384

African (AFR) AF: 0.206 AC: 8559 AN: 41534

American (AMR) AF: 0.323 AC: 4938 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1805 AN: 5162

South Asian (SAS) AF: 0.316 AC: 1521 AN: 4820

European-Finnish (FIN) AF: 0.326 AC: 3449 AN: 10590

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23629 AN: 67992

Other (OTH) AF: 0.313 AC: 659 AN: 2108

Alfa AF: 0.335 Hom.: 26672

Bravo AF: 0.301

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.97
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: rs12045440; hg19: chr1-19765518;