rs1488009

Positions:

• chr7-130318258-G-A
• chr7-130318258-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016352.4(CPA4):​c.1079-4231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,064 control chromosomes in the GnomAD database, including 59,324 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 0.88 (59324 hom., cov: 30)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

Genes affected

CPA4 (HGNC:15740): (carboxypeptidase A4) This gene is a member of the carboxypeptidase A/B subfamily, and it is located in a cluster with three other family members on chromosome 7. Carboxypeptidases are zinc-containing exopeptidases that catalyze the release of carboxy-terminal amino acids, and are synthesized as zymogens that are activated by proteolytic cleavage. This gene could be involved in the histone hyperacetylation pathway. It is imprinted and may be a strong candidate gene for prostate cancer aggressiveness. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA4	NM_016352.4	c.1079-4231G>A		intron_variant		ENST00000222482.10
CPA4	NM_001163446.2	c.980-4231G>A		intron_variant
CPA4	XM_047420438.1	c.767-4231G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA4	ENST00000222482.10	c.1079-4231G>A		intron_variant		1	NM_016352.4	P1
CPA4	ENST00000445470.6	c.980-4231G>A		intron_variant		2
CPA4	ENST00000493259.5	c.767-4231G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133923 AN: 151946 Hom.: 59286 Cov.: 30

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.888

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

GnomAD4 genome AF: 0.881 AC: 134019 AN: 152064 Hom.: 59324 Cov.: 30 AF XY: 0.888 AC XY: 66031 AN XY: 74330

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.967

Gnomad4 FIN AF: 0.936

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.889

Alfa AF: 0.897 Hom.: 81146

Bravo AF: 0.877

Asia WGS AF: 0.968 AC: 3367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs1488009; hg19: chr7-129958098;