7-130318327-T-C

Variant names:

• chr7-130318327-T-C
• rs3800775
• NM_016352.4:c.1079-4162T>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.1079-4162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,010 control chromosomes in the GnomAD database, including 30,422 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 0.63 (30422 hom., cov: 32)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.676 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	NM_016352.4	MANE Select	c.1079-4162T>C		intron	N/A	NP_057436.2	A4D1M3
	CPA4	NM_001163446.2		c.980-4162T>C		intron	N/A	NP_001156918.1	Q9UI42-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	ENST00000222482.10	TSL:1 MANE Select	c.1079-4162T>C		intron	N/A	ENSP00000222482.4	Q9UI42-1
	CPA4	ENST00000445470.6	TSL:2	c.980-4162T>C		intron	N/A	ENSP00000412947.2	Q9UI42-2
	CPA4	ENST00000493259.5	TSL:2	c.767-4162T>C		intron	N/A	ENSP00000419660.1	B7Z5J4

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96034 AN: 151892 Hom.: 30395 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.632 AC: 96116 AN: 152010 Hom.: 30422 Cov.: 32 AF XY: 0.635 AC XY: 47151 AN XY: 74308

African (AFR) AF: 0.643 AC: 26668 AN: 41460

American (AMR) AF: 0.687 AC: 10499 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2323 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3293 AN: 5166

South Asian (SAS) AF: 0.643 AC: 3090 AN: 4808

European-Finnish (FIN) AF: 0.639 AC: 6742 AN: 10552

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41445 AN: 67960

Other (OTH) AF: 0.631 AC: 1334 AN: 2114

Alfa AF: 0.619 Hom.: 88521

Bravo AF: 0.637

Asia WGS AF: 0.620 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.41
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3800775; hg19: chr7-129958167;