chr7-130344948-G-A

Position:

• chr7-130344948-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_080385.5(CPA5):​c.-409G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,002 control chromosomes in the GnomAD database, including 27,590 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 0.60 (27590 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CPA5 NM_080385.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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]

LOC105375503 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA5	NM_080385.5	c.-409G>A		5_prime_UTR_variant	1/13	ENST00000474905.6
LOC105375503	XR_001745362.2	n.103+6581C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA5	ENST00000474905.6	c.-409G>A		5_prime_UTR_variant	1/13	1	NM_080385.5	P1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91226 AN: 151884 Hom.: 27573 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.602

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.601 AC: 91289 AN: 152002 Hom.: 27590 Cov.: 32 AF XY: 0.597 AC XY: 44355 AN XY: 74282

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.604

Alfa AF: 0.568 Hom.: 11921

Bravo AF: 0.607

Asia WGS AF: 0.512 AC: 1780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.64

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: rs1532047; hg19: chr7-129984788;