rs10504402

chr8-67577929-A-T

Variant summary

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

The NM_020361.5(CPA6):c.192+46247T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 152,306 control chromosomes in the GnomAD database, including 52 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 0.0074 (52 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561

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]

LOC105375886 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA6	NM_020361.5	c.192+46247T>A		intron_variant		ENST00000297770.10
LOC105375886	XR_007060953.1	n.175+21472A>T		intron_variant, non_coding_transcript_variant
CPA6	XM_017013646.2	c.-128+46247T>A		intron_variant
CPA6	XM_017013647.2	c.192+46247T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA6	ENST00000297770.10	c.192+46247T>A		intron_variant		1	NM_020361.5	P1
CPA6	ENST00000479862.6	c.192+46247T>A		intron_variant, NMD_transcript_variant		1
CPA6	ENST00000518549.1	n.406+46247T>A		intron_variant, non_coding_transcript_variant		1
CPA6	ENST00000638254.1	c.192+46247T>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00737 AC: 1121 AN: 152188 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.00431

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

GnomAD4 genome AF: 0.00736 AC: 1121 AN: 152306 Hom.: 52 Cov.: 32 AF XY: 0.00819 AC XY: 610 AN XY: 74470

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00310

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00424 Hom.: 0

Bravo AF: 0.00702

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	9.6
Dann	Benign	0.84

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: rs10504402; hg19: chr8-68490164;