7-130296035-T-C

Position:

• chr7-130296035-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.69-2711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,130 control chromosomes in the GnomAD database, including 9,420 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 0.35 (9420 hom., cov: 33)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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]

CPA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA4	NM_016352.4	c.69-2711T>C		intron_variant		ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2	c.69-2711T>C		intron_variant			NP_001156918.1
CPA4	XM_047420438.1	c.-245+2520T>C		intron_variant			XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.69-2711T>C		intron_variant		1	NM_016352.4	ENSP00000222482.4

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52691 AN: 152012 Hom.: 9401 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.347 AC: 52753 AN: 152130 Hom.: 9420 Cov.: 33 AF XY: 0.354 AC XY: 26295 AN XY: 74360

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.343

Alfa AF: 0.352 Hom.: 2064

Bravo AF: 0.349

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
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: rs6942830; hg19: chr7-129935875;