rs750564641

Variant names:

• chr1-19342853-G-A
• rs750564641
• ENST00000375144.6:c.*1501C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001206540.3(CAPZB):​c.743C>T​(p.Ala248Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAPZB NM_001206540.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.71
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14510149).
• BP6: Variant 1-19342853-G-A is Benign according to our data. Variant chr1-19342853-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3484936.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206540.3. 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.731+1505C>T		intron	N/A	NP_004921.1	A0A384MR50
	CAPZB	NM_001206540.3		c.743C>T	p.Ala248Val	missense	Exon 9 of 10	NP_001193469.1	P47756-1
	CAPZB	NM_001282162.2		c.818+1505C>T		intron	N/A	NP_001269091.1	B1AK88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZB	ENST00000375144.6	TSL:1	c.*1501C>T		3_prime_UTR	Exon 8 of 8	ENSP00000364286.2	B1AK87
	CAPZB	ENST00000264202.8	TSL:1 MANE Select	c.731+1505C>T		intron	N/A	ENSP00000264202.7	P47756-2
	CAPZB	ENST00000375142.6	TSL:5	c.743C>T	p.Ala248Val	missense	Exon 9 of 10	ENSP00000364284.1	P47756-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000828 AC: 2 AN: 241480 AF XY: 0.00000754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000933

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446234 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 720496

African (AFR) AF: 0.00 AC: 0 AN: 33014

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099038

Other (OTH) AF: 0.00 AC: 0 AN: 59830

GnomAD4 genome Cov.: 32

Alfa AF: 0.000223 Hom.: 0

ExAC AF: 0.00000855 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.072
Sift	Benign	0.16	T
Sift4G	Benign	0.22	T
Vest4		0.086
MutPred		0.25		Loss of disorder (P = 0.1599)
MVP		0.46
MPC		0.021
ClinPred		0.30	T
GERP RS		4.6
Varity_R		0.063
Mutation Taster		=87/13	polymorphism

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: rs750564641; hg19: chr1-19669347;