rs4731688

Positions:

• chr7-130357220-A-G

Variant summary

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

The NM_080385.5(CPA5):​c.334-2369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,070 control chromosomes in the GnomAD database, including 5,217 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 0.23 (5217 hom., cov: 32)
• Consequence: CPA5 NM_080385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843

Genes affected

CPA5 (HGNC:15722): (carboxypeptidase A5) Carboxypeptidases have functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Members of the A/B subfamily of carboxypeptidases, such as CPA5, contain an approximately 90-amino acid pro region that assists in the folding of the active carboxypeptidase domain. Cleavage of the pro region activates the enzyme (Wei et al., 2002 [PubMed 11836249]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA5	NM_080385.5	c.334-2369A>G		intron_variant		ENST00000474905.6	NP_525124.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA5	ENST00000474905.6	c.334-2369A>G		intron_variant		1	NM_080385.5	ENSP00000417314	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34921 AN: 151952 Hom.: 5207 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.230 AC: 34967 AN: 152070 Hom.: 5217 Cov.: 32 AF XY: 0.222 AC XY: 16497 AN XY: 74344

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.208

Alfa AF: 0.198 Hom.: 720

Bravo AF: 0.237

Asia WGS AF: 0.0810 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.44

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: rs4731688; hg19: chr7-129997061;