rs10808755

chr8-67604446-G-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+19730C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,966 control chromosomes in the GnomAD database, including 26,321 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 0.56 (26321 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA6	NM_020361.5	c.192+19730C>A		intron_variant		ENST00000297770.10
LOC105375886	XR_007060953.1	n.176-2328G>T		intron_variant, non_coding_transcript_variant
CPA6	XM_017013646.2	c.-128+19730C>A		intron_variant
CPA6	XM_017013647.2	c.192+19730C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA6	ENST00000297770.10	c.192+19730C>A		intron_variant		1	NM_020361.5	P1
CPA6	ENST00000479862.6	c.192+19730C>A		intron_variant, NMD_transcript_variant		1
CPA6	ENST00000518549.1	n.406+19730C>A		intron_variant, non_coding_transcript_variant		1
CPA6	ENST00000638254.1	c.192+19730C>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85113 AN: 151848 Hom.: 26270 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.561 AC: 85223 AN: 151966 Hom.: 26321 Cov.: 32 AF XY: 0.560 AC XY: 41600 AN XY: 74258

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.522

Alfa AF: 0.460 Hom.: 22036

Bravo AF: 0.589

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.41
Dann	Benign	0.20

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: rs10808755; hg19: chr8-68516681;