chr1-112648185-A-C

Variant names:

• chr1-112648185-A-C
• rs17030613
• NM_006135.3:c.103+912A>C

Variant summary

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

The NM_006135.3(CAPZA1):​c.103+912A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,952 control chromosomes in the GnomAD database, including 3,780 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 0.20 (3780 hom., cov: 31)
• Consequence: CAPZA1 NM_006135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 55 publications found

Genes affected

CAPZA1 (HGNC:1488): (capping actin protein of muscle Z-line subunit alpha 1) CAPZA1 is a member of the F-actin capping protein alpha subunit family. This gene encodes the alpha subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPZA1	NM_006135.3	c.103+912A>C		intron_variant	Intron 2 of 9	ENST00000263168.4	NP_006126.1
CAPZA1	XM_017002424.3	c.103+912A>C		intron_variant	Intron 2 of 9		XP_016857913.1
CAPZA1	XM_011542225.4	c.103+912A>C		intron_variant	Intron 2 of 8		XP_011540527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPZA1	ENST00000263168.4	c.103+912A>C		intron_variant	Intron 2 of 9	1	NM_006135.3	ENSP00000263168.3
CAPZA1	ENST00000476936.5	n.129+912A>C		intron_variant	Intron 2 of 7	3
CAPZA1	ENST00000485542.5	n.143+912A>C		intron_variant	Intron 2 of 2	2
CAPZA1	ENST00000498626.1	n.156+912A>C		intron_variant	Intron 3 of 8	5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29914 AN: 151834 Hom.: 3778 Cov.: 31

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.197 AC: 29923 AN: 151952 Hom.: 3780 Cov.: 31 AF XY: 0.209 AC XY: 15506 AN XY: 74212

African (AFR) AF: 0.0774 AC: 3213 AN: 41506

American (AMR) AF: 0.257 AC: 3923 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2440 AN: 5156

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4816

European-Finnish (FIN) AF: 0.376 AC: 3948 AN: 10494

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13763 AN: 67948

Other (OTH) AF: 0.188 AC: 397 AN: 2110

Alfa AF: 0.212 Hom.: 12659

Bravo AF: 0.189

Asia WGS AF: 0.318 AC: 1101 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		0.20
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: rs17030613; hg19: chr1-113190807;