chr7-130298204-T-C

Variant names:

• chr7-130298204-T-C
• rs1569132
• NM_016352.4:c.69-542T>C

Variant summary

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

The NM_016352.4(CPA4):​c.69-542T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,032 control chromosomes in the GnomAD database, including 12,963 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 0.41 (12963 hom., cov: 32)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA4	NM_016352.4	c.69-542T>C		intron_variant	Intron 1 of 10	ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2	c.69-542T>C		intron_variant	Intron 1 of 9		NP_001156918.1
CPA4	XM_047420438.1	c.-244-542T>C		intron_variant	Intron 1 of 10		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.69-542T>C		intron_variant	Intron 1 of 10	1	NM_016352.4	ENSP00000222482.4

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62780 AN: 151914 Hom.: 12948 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.413 AC: 62829 AN: 152032 Hom.: 12963 Cov.: 32 AF XY: 0.409 AC XY: 30394 AN XY: 74330

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.408

Alfa AF: 0.416 Hom.: 4054

Bravo AF: 0.411

Asia WGS AF: 0.420 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.35

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: rs1569132; hg19: chr7-129938044;