rs1503369

Positions:

• chr8-67509763-T-C

Variant summary

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

The NM_020361.5(CPA6):​c.433-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 465,930 control chromosomes in the GnomAD database, including 39,952 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 0.46 (17656 hom., cov: 32)
  • Exomes 𝑓: 0.36 (22296 hom.)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

Genes affected

CPA6 (HGNC:17245): (carboxypeptidase A6) The gene encodes a member of the peptidase M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature enzyme, which catalyzes the release of large hydrophobic C-terminal amino acids. This enzyme has functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Mutations in this gene may be linked to epilepsy and febrile seizures, and a translocation t(6;8)(q26;q13) involving this gene has been associated with Duane retraction syndrome. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA6	NM_020361.5	c.433-145A>G		intron_variant		ENST00000297770.10
CPA6	XM_017013646.2	c.-12-145A>G		intron_variant
CPA6	XM_017013647.2	c.433-145A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA6	ENST00000297770.10	c.433-145A>G		intron_variant		1	NM_020361.5	P1
CPA6	ENST00000479862.6	c.*29-145A>G		intron_variant, NMD_transcript_variant		1
CPA6	ENST00000518549.1	n.647-145A>G		intron_variant, non_coding_transcript_variant		1
CPA6	ENST00000638254.1	c.*29-145A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69757 AN: 151922 Hom.: 17619 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.454

GnomAD4 exome AF: 0.364 AC: 114396 AN: 313890 Hom.: 22296 AF XY: 0.363 AC XY: 58980 AN XY: 162320

Gnomad4 AFR exome AF: 0.694

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.459 AC: 69835 AN: 152040 Hom.: 17656 Cov.: 32 AF XY: 0.455 AC XY: 33804 AN XY: 74310

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.448

Alfa AF: 0.401 Hom.: 1663

Bravo AF: 0.476

Asia WGS AF: 0.334 AC: 1153 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.47

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: rs1503369; hg19: chr8-68421998;