7-130296035-T-C

Variant names:

• chr7-130296035-T-C
• rs6942830
• NM_016352.4:c.69-2711T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016352.4(CPA4):​c.69-2711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,130 control chromosomes in the GnomAD database, including 9,420 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 0.35 (9420 hom., cov: 33)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016352.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	NM_016352.4	MANE Select	c.69-2711T>C		intron	N/A	NP_057436.2
	CPA4	NM_001163446.2		c.69-2711T>C		intron	N/A	NP_001156918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	ENST00000222482.10	TSL:1 MANE Select	c.69-2711T>C		intron	N/A	ENSP00000222482.4
	CPA4	ENST00000474254.5	TSL:1	n.89-2711T>C		intron	N/A
	CPA4	ENST00000445470.6	TSL:2	c.69-2711T>C		intron	N/A	ENSP00000412947.2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52691 AN: 152012 Hom.: 9401 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.347 AC: 52753 AN: 152130 Hom.: 9420 Cov.: 33 AF XY: 0.354 AC XY: 26295 AN XY: 74360

African (AFR) AF: 0.280 AC: 11630 AN: 41500

American (AMR) AF: 0.441 AC: 6738 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3472

East Asian (EAS) AF: 0.494 AC: 2561 AN: 5184

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4822

European-Finnish (FIN) AF: 0.410 AC: 4334 AN: 10566

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23364 AN: 67986

Other (OTH) AF: 0.343 AC: 726 AN: 2116

Alfa AF: 0.356 Hom.: 3776

Bravo AF: 0.349

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.61
PhyloP100		-0.21
Mutation Taster		=100/0	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: rs6942830; hg19: chr7-129935875;