7-130305154-A-G

Variant names:

• chr7-130305154-A-G
• rs1038627
• NM_016352.4:c.486+575A>G

Variant summary

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

The NM_016352.4(CPA4):​c.486+575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,124 control chromosomes in the GnomAD database, including 14,131 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 0.43 (14131 hom., cov: 33)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 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.486+575A>G		intron	N/A	NP_057436.2
	CPA4	NM_001163446.2		c.387+575A>G		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.486+575A>G		intron	N/A	ENSP00000222482.4
	CPA4	ENST00000474254.5	TSL:1	n.565+575A>G		intron	N/A
	CPA4	ENST00000445470.6	TSL:2	c.387+575A>G		intron	N/A	ENSP00000412947.2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65242 AN: 152006 Hom.: 14100 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.429 AC: 65315 AN: 152124 Hom.: 14131 Cov.: 33 AF XY: 0.425 AC XY: 31616 AN XY: 74370

African (AFR) AF: 0.470 AC: 19478 AN: 41482

American (AMR) AF: 0.359 AC: 5491 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1803 AN: 5180

South Asian (SAS) AF: 0.398 AC: 1922 AN: 4824

European-Finnish (FIN) AF: 0.394 AC: 4164 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29646 AN: 67974

Other (OTH) AF: 0.415 AC: 876 AN: 2112

Alfa AF: 0.427 Hom.: 44422

Bravo AF: 0.428

Asia WGS AF: 0.421 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		0.098
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: rs1038627; hg19: chr7-129944994;