rs1949350

Positions:

• chr3-148888938-G-C

Variant summary

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

The NM_001870.4(CPA3):​c.1066+2761G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,078 control chromosomes in the GnomAD database, including 30,590 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 0.63 (30590 hom., cov: 32)
• Consequence: CPA3 NM_001870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

Genes affected

CPA3 (HGNC:2298): (carboxypeptidase A3) This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. The encoded preproprotein is proteolytically processed to generate a mature protease that is released by mast cells and may be involved in the degradation of endogenous proteins and the inactivation of venom-associated peptides. Expression of this gene may be elevated in human asthma patients. [provided by RefSeq, Nov 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA3	NM_001870.4	c.1066+2761G>C		intron_variant		ENST00000296046.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA3	ENST00000296046.4	c.1066+2761G>C		intron_variant		1	NM_001870.4	P1
	ENST00000488190.1	n.163-18849C>G		intron_variant, non_coding_transcript_variant		1
CPA3	ENST00000477926.1	n.543+2761G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96166 AN: 151960 Hom.: 30563 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.633 AC: 96236 AN: 152078 Hom.: 30590 Cov.: 32 AF XY: 0.634 AC XY: 47152 AN XY: 74334

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.645

Alfa AF: 0.644 Hom.: 3931

Bravo AF: 0.630

Asia WGS AF: 0.611 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.42

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: rs1949350; hg19: chr3-148606725;