1-19356807-G-T

Variant names:

• chr1-19356807-G-T
• rs169957
• NM_004930.5:c.472-56C>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.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
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZB	NM_004930.5	MANE Select	c.472-56C>A		intron	N/A	NP_004921.1
	CAPZB	NM_001282162.2		c.559-56C>A		intron	N/A	NP_001269091.1
	CAPZB	NM_001206540.3		c.472-56C>A		intron	N/A	NP_001193469.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZB	ENST00000264202.8	TSL:1 MANE Select	c.472-56C>A		intron	N/A	ENSP00000264202.7
	CAPZB	ENST00000375144.6	TSL:1	c.472-56C>A		intron	N/A	ENSP00000364286.2
	CAPZB	ENST00000433834.5	TSL:2	c.559-56C>A		intron	N/A	ENSP00000401010.1

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

African (AFR) AF: 0.516 AC: 12516 AN: 24250

American (AMR) AF: 0.522 AC: 21271 AN: 40776

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 9214 AN: 21448

East Asian (EAS) AF: 0.602 AC: 22456 AN: 37292

South Asian (SAS) AF: 0.375 AC: 27589 AN: 73610

European-Finnish (FIN) AF: 0.429 AC: 21441 AN: 49944

Middle Eastern (MID) AF: 0.416 AC: 1964 AN: 4724

European-Non Finnish (NFE) AF: 0.411 AC: 286784 AN: 697234

Other (OTH) AF: 0.430 AC: 19156 AN: 44550

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

African (AFR) AF: 0.510 AC: 21096 AN: 41392

American (AMR) AF: 0.511 AC: 7804 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3468

East Asian (EAS) AF: 0.558 AC: 2884 AN: 5172

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4814

European-Finnish (FIN) AF: 0.428 AC: 4510 AN: 10542

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27835 AN: 67930

Other (OTH) AF: 0.452 AC: 953 AN: 2110

Alfa AF: 0.423 Hom.: 34025

Bravo AF: 0.462

Asia WGS AF: 0.483 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.046
DANN	Benign	0.60
PhyloP100		-0.55
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: rs169957; hg19: chr1-19683301;