7-130294379-T-C

Position:

• chr7-130294379-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.68+1131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,066 control chromosomes in the GnomAD database, including 10,200 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 0.36 (10200 hom., cov: 32)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA4	NM_016352.4	c.68+1131T>C		intron_variant		ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2	c.68+1131T>C		intron_variant			NP_001156918.1
CPA4	XM_047420438.1	c.-245+864T>C		intron_variant			XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.68+1131T>C		intron_variant		1	NM_016352.4	ENSP00000222482	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54983 AN: 151948 Hom.: 10180 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.362 AC: 55047 AN: 152066 Hom.: 10200 Cov.: 32 AF XY: 0.367 AC XY: 27303 AN XY: 74334

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.350

Alfa AF: 0.351 Hom.: 15492

Bravo AF: 0.366

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.62

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: rs3807344; hg19: chr7-129934219; COSMIC: COSV55978818; COSMIC: COSV55978818;