8-67552111-G-T

Position:

• chr8-67552111-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.193-34064C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,152 control chromosomes in the GnomAD database, including 43,500 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 0.75 (43500 hom., cov: 34)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

CPA6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA6	NM_020361.5	c.193-34064C>A		intron_variant		ENST00000297770.10	NP_065094.3
CPA6	XM_017013646.2	c.-127-40456C>A		intron_variant			XP_016869135.1
CPA6	XM_017013647.2	c.193-34064C>A		intron_variant			XP_016869136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA6	ENST00000297770.10	c.193-34064C>A		intron_variant		1	NM_020361.5	ENSP00000297770.4
CPA6	ENST00000479862.6	n.193-40456C>A		intron_variant		1		ENSP00000419016.2
CPA6	ENST00000518549.1	n.407-34064C>A		intron_variant		1
CPA6	ENST00000638254.1	n.193-40456C>A		intron_variant		5		ENSP00000491129.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114488 AN: 152034 Hom.: 43466 Cov.: 34

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.753 AC: 114574 AN: 152152 Hom.: 43500 Cov.: 34 AF XY: 0.750 AC XY: 55801 AN XY: 74384

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.764

Alfa AF: 0.779 Hom.: 21091

Bravo AF: 0.753

Asia WGS AF: 0.708 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.7
DANN	Benign	0.62

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: rs924740; hg19: chr8-68464346;