8-67509330-A-G

Variant names:

• chr8-67509330-A-G
• rs1393902
• NM_020361.5:c.534+187T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020361.5(CPA6):​c.534+187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,066 control chromosomes in the GnomAD database, including 17,601 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 (17601 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• benign familial mesial temporal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial mesial temporal lobe epilepsy with febrile seizures

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial temporal lobe epilepsy 5

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 11

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy

  Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020361.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA6	NM_020361.5	MANE Select	c.534+187T>C		intron	N/A	NP_065094.3
	CPA6	NM_001440615.1		c.534+187T>C		intron	N/A	NP_001427544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA6	ENST00000297770.10	TSL:1 MANE Select	c.534+187T>C		intron	N/A	ENSP00000297770.4
	CPA6	ENST00000479862.6	TSL:1	n.*130+187T>C		intron	N/A	ENSP00000419016.2
	CPA6	ENST00000518549.1	TSL:1	n.748+187T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69617 AN: 151944 Hom.: 17563 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.458 AC: 69697 AN: 152066 Hom.: 17601 Cov.: 32 AF XY: 0.454 AC XY: 33750 AN XY: 74340

African (AFR) AF: 0.699 AC: 29000 AN: 41494

American (AMR) AF: 0.372 AC: 5675 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1977 AN: 5172

South Asian (SAS) AF: 0.355 AC: 1710 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3848 AN: 10568

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24674 AN: 67966

Other (OTH) AF: 0.448 AC: 944 AN: 2108

Alfa AF: 0.412 Hom.: 1838

Bravo AF: 0.475

Asia WGS AF: 0.337 AC: 1170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.58
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1393902; hg19: chr8-68421565;