rs2306848

Positions:

• chr7-130322574-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_016352.4(CPA4):​c.1164C>T​(p.Thr388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 1,614,002 control chromosomes in the GnomAD database, including 4,175 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 0.066 (360 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3815 hom.)
• Consequence: CPA4 NM_016352.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

LOC105375503 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.147 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA4	NM_016352.4	c.1164C>T	p.Thr388=	synonymous_variant	11/11	ENST00000222482.10	NP_057436.2
LOC105375503	XR_001745362.2	n.104-1809G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.1164C>T	p.Thr388=	synonymous_variant	11/11	1	NM_016352.4	ENSP00000222482	P1
CPA4	ENST00000445470.6	c.1065C>T	p.Thr355=	synonymous_variant	10/10	2		ENSP00000412947
CPA4	ENST00000493259.5	c.852C>T	p.Thr284=	synonymous_variant	9/9	2		ENSP00000419660

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 10003 AN: 152152 Hom.: 358 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0737

GnomAD3 exomes AF: 0.0571 AC: 14359 AN: 251342 Hom.: 460 AF XY: 0.0580 AC XY: 7872 AN XY: 135828

Gnomad AFR exome AF: 0.0613

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.0712

Gnomad EAS exome AF: 0.0156

Gnomad SAS exome AF: 0.0303

Gnomad FIN exome AF: 0.0548

Gnomad NFE exome AF: 0.0765

Gnomad OTH exome AF: 0.0629

GnomAD4 exome AF: 0.0702 AC: 102601 AN: 1461732 Hom.: 3815 Cov.: 33 AF XY: 0.0687 AC XY: 49957 AN XY: 727200

Gnomad4 AFR exome AF: 0.0655

Gnomad4 AMR exome AF: 0.0372

Gnomad4 ASJ exome AF: 0.0739

Gnomad4 EAS exome AF: 0.0179

Gnomad4 SAS exome AF: 0.0316

Gnomad4 FIN exome AF: 0.0562

Gnomad4 NFE exome AF: 0.0773

Gnomad4 OTH exome AF: 0.0662

GnomAD4 genome AF: 0.0658 AC: 10019 AN: 152270 Hom.: 360 Cov.: 32 AF XY: 0.0625 AC XY: 4654 AN XY: 74458

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.0482

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0733 Hom.: 712

Bravo AF: 0.0653

Asia WGS AF: 0.0200 AC: 70 AN: 3478

EpiCase AF: 0.0775

EpiControl AF: 0.0744

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.3
DANN	Benign	0.80

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: rs2306848; hg19: chr7-129962414; COSMIC: COSV55984499;