rs1393901

Variant names:

• chr8-67513099-T-C
• rs1393901
• NM_020361.5:c.318-1444A>G

Variant summary

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

The NM_020361.5(CPA6):​c.318-1444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,994 control chromosomes in the GnomAD database, including 17,300 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 (17300 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA6	NM_020361.5	MANE Select	c.318-1444A>G		intron	N/A	NP_065094.3
	CPA6	NM_001440615.1		c.318-1444A>G		intron	N/A	NP_001427544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA6	ENST00000297770.10	TSL:1 MANE Select	c.318-1444A>G		intron	N/A	ENSP00000297770.4	Q8N4T0-1
	CPA6	ENST00000479862.6	TSL:1	n.193-1444A>G		intron	N/A	ENSP00000419016.2	Q8N4T0-3
	CPA6	ENST00000518549.1	TSL:1	n.532-1444A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69235 AN: 151876 Hom.: 17270 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.456 AC: 69306 AN: 151994 Hom.: 17300 Cov.: 32 AF XY: 0.452 AC XY: 33563 AN XY: 74304

African (AFR) AF: 0.687 AC: 28449 AN: 41428

American (AMR) AF: 0.370 AC: 5653 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1961 AN: 5172

South Asian (SAS) AF: 0.354 AC: 1707 AN: 4826

European-Finnish (FIN) AF: 0.365 AC: 3854 AN: 10556

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24834 AN: 67964

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.388 Hom.: 5402

Bravo AF: 0.472

Asia WGS AF: 0.336 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.73
PhyloP100		0.063
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: rs1393901; hg19: chr8-68425334; COSMIC: COSV52740921;