rs1038628

Positions:

• chr7-130308173-G-T

Variant summary

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

The NM_016352.4(CPA4):​c.703-134G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 724,972 control chromosomes in the GnomAD database, including 49,622 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 0.33 (8861 hom., cov: 32)
  • Exomes 𝑓: 0.37 (40761 hom.)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA4	NM_016352.4	c.703-134G>T		intron_variant		ENST00000222482.10
CPA4	NM_001163446.2	c.604-134G>T		intron_variant
CPA4	XM_047420438.1	c.391-134G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA4	ENST00000222482.10	c.703-134G>T		intron_variant		1	NM_016352.4	P1
CPA4	ENST00000445470.6	c.604-134G>T		intron_variant		2
CPA4	ENST00000493259.5	c.391-134G>T		intron_variant		2
CPA4	ENST00000488025.1	n.42G>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50566 AN: 151924 Hom.: 8861 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.373 AC: 213783 AN: 572930 Hom.: 40761 Cov.: 6 AF XY: 0.374 AC XY: 115092 AN XY: 307368

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.333 AC: 50584 AN: 152042 Hom.: 8861 Cov.: 32 AF XY: 0.334 AC XY: 24810 AN XY: 74278

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.341

Alfa AF: 0.357 Hom.: 1271

Bravo AF: 0.323

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.79

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: rs1038628; hg19: chr7-129948013; COSMIC: COSV55983792; COSMIC: COSV55983792;