7-130318327-T-C

Position:

• chr7-130318327-T-C

Variant summary

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

The NM_016352.4(CPA4):​c.1079-4162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,010 control chromosomes in the GnomAD database, including 30,422 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 0.63 (30422 hom., cov: 32)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA4	NM_016352.4	c.1079-4162T>C		intron_variant		ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2	c.980-4162T>C		intron_variant			NP_001156918.1
CPA4	XM_047420438.1	c.767-4162T>C		intron_variant			XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.1079-4162T>C		intron_variant		1	NM_016352.4	ENSP00000222482.4
CPA4	ENST00000445470.6	c.980-4162T>C		intron_variant		2		ENSP00000412947.2
CPA4	ENST00000493259.5	c.767-4162T>C		intron_variant		2		ENSP00000419660.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96034 AN: 151892 Hom.: 30395 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.632 AC: 96116 AN: 152010 Hom.: 30422 Cov.: 32 AF XY: 0.635 AC XY: 47151 AN XY: 74308

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.631

Alfa AF: 0.614 Hom.: 57129

Bravo AF: 0.637

Asia WGS AF: 0.620 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3800775; hg19: chr7-129958167;