chr8-67513007-A-G

Variant names:

• chr8-67513007-A-G
• rs1827524
• NM_020361.5:c.318-1352T>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.318-1352T>C 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 152,086 control chromosomes in the GnomAD database, including 17,359 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 (17359 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 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.318-1352T>C		intron	N/A	NP_065094.3
	CPA6	NM_001440615.1		c.318-1352T>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.318-1352T>C		intron	N/A	ENSP00000297770.4
	CPA6	ENST00000479862.6	TSL:1	n.193-1352T>C		intron	N/A	ENSP00000419016.2
	CPA6	ENST00000518549.1	TSL:1	n.532-1352T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69343 AN: 151966 Hom.: 17326 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.456 AC: 69418 AN: 152086 Hom.: 17359 Cov.: 32 AF XY: 0.452 AC XY: 33628 AN XY: 74356

African (AFR) AF: 0.689 AC: 28571 AN: 41464

American (AMR) AF: 0.370 AC: 5647 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3464

East Asian (EAS) AF: 0.378 AC: 1956 AN: 5170

South Asian (SAS) AF: 0.353 AC: 1708 AN: 4832

European-Finnish (FIN) AF: 0.365 AC: 3855 AN: 10568

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

European-Non Finnish (NFE) AF: 0.365 AC: 24836 AN: 67994

Other (OTH) AF: 0.448 AC: 947 AN: 2112

Alfa AF: 0.275 Hom.: 733

Bravo AF: 0.473

Asia WGS AF: 0.337 AC: 1168 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.38
DANN	Benign	0.60
PhyloP100		-0.97
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: rs1827524; hg19: chr8-68425242;