rs2306848

Variant names:

• chr7-130322574-C-T
• rs2306848
• NM_016352.4:c.1164C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_016352.4(CPA4):​c.1164C>T​(p.Thr388Thr) 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPA4	NM_016352.4	c.1164C>T	p.Thr388Thr	synonymous_variant	Exon 11 of 11	ENST00000222482.10	NP_057436.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.1164C>T	p.Thr388Thr	synonymous_variant	Exon 11 of 11	1	NM_016352.4	ENSP00000222482.4
CPA4	ENST00000445470.6	c.1065C>T	p.Thr355Thr	synonymous_variant	Exon 10 of 10	2		ENSP00000412947.2
CPA4	ENST00000493259.5	c.852C>T	p.Thr284Thr	synonymous_variant	Exon 9 of 9	2		ENSP00000419660.1

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

GnomAD2 exomes AF: 0.0571 AC: 14359 AN: 251342 AF XY: 0.0580

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 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

African (AFR) AF: 0.0655 AC: 2192 AN: 33472

American (AMR) AF: 0.0372 AC: 1662 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0739 AC: 1931 AN: 26136

East Asian (EAS) AF: 0.0179 AC: 709 AN: 39698

South Asian (SAS) AF: 0.0316 AC: 2724 AN: 86250

European-Finnish (FIN) AF: 0.0562 AC: 3002 AN: 53416

Middle Eastern (MID) AF: 0.0687 AC: 396 AN: 5768

European-Non Finnish (NFE) AF: 0.0773 AC: 85990 AN: 1111882

Other (OTH) AF: 0.0662 AC: 3995 AN: 60390

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

African (AFR) AF: 0.0659 AC: 2737 AN: 41550

American (AMR) AF: 0.0482 AC: 738 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3472

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5188

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4820

European-Finnish (FIN) AF: 0.0515 AC: 546 AN: 10612

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0785 AC: 5335 AN: 68002

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0729 Hom.: 840

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
PhyloP100		0.15
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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