rs4731688

Variant names:

• chr7-130357220-A-G
• rs4731688
• NM_080385.5:c.334-2369A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPA5	NM_080385.5	c.334-2369A>G		intron_variant	Intron 5 of 12	ENST00000474905.6	NP_525124.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA5	ENST00000474905.6	c.334-2369A>G		intron_variant	Intron 5 of 12	1	NM_080385.5	ENSP00000417314.1

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

African (AFR) AF: 0.427 AC: 17681 AN: 41426

American (AMR) AF: 0.152 AC: 2315 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5184

South Asian (SAS) AF: 0.121 AC: 581 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1662 AN: 10590

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11567 AN: 67982

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.203 Hom.: 778

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
PhyloP100		0.84
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: rs4731688; hg19: chr7-129997061;