NM_020361.5:c.193-34064C>A

Variant names:

• chr8-67552111-G-T
• rs924740
• NM_020361.5:c.193-34064C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 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.193-34064C>A		intron	N/A	NP_065094.3
	CPA6	NM_001440615.1		c.193-34064C>A		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.193-34064C>A		intron	N/A	ENSP00000297770.4
	CPA6	ENST00000479862.6	TSL:1	n.193-40456C>A		intron	N/A	ENSP00000419016.2
	CPA6	ENST00000518549.1	TSL:1	n.407-34064C>A		intron	N/A

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

African (AFR) AF: 0.678 AC: 28131 AN: 41484

American (AMR) AF: 0.778 AC: 11899 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2644 AN: 3472

East Asian (EAS) AF: 0.749 AC: 3873 AN: 5174

South Asian (SAS) AF: 0.655 AC: 3157 AN: 4820

European-Finnish (FIN) AF: 0.762 AC: 8071 AN: 10590

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.798 AC: 54277 AN: 68004

Other (OTH) AF: 0.764 AC: 1613 AN: 2110

Alfa AF: 0.780 Hom.: 23507

Bravo AF: 0.753

Asia WGS AF: 0.708 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.7
DANN	Benign	0.62
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs924740; hg19: chr8-68464346;