rs10808755

Variant names:

• chr8-67604446-G-T
• rs10808755
• NM_020361.5:c.192+19730C>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.192+19730C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,966 control chromosomes in the GnomAD database, including 26,321 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 0.56 (26321 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• 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

LOC105375886 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA6	NM_020361.5	c.192+19730C>A		intron_variant	Intron 2 of 10	ENST00000297770.10	NP_065094.3
CPA6	NM_001440615.1	c.192+19730C>A		intron_variant	Intron 2 of 6		NP_001427544.1
CPA6	XM_017013646.2	c.-128+19730C>A		intron_variant	Intron 3 of 10		XP_016869135.1
LOC105375886	XR_007060953.1	n.176-2328G>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA6	ENST00000297770.10	c.192+19730C>A		intron_variant	Intron 2 of 10	1	NM_020361.5	ENSP00000297770.4
CPA6	ENST00000479862.6	n.192+19730C>A		intron_variant	Intron 2 of 7	1		ENSP00000419016.2
CPA6	ENST00000518549.1	n.406+19730C>A		intron_variant	Intron 2 of 7	1
CPA6	ENST00000638254.1	n.192+19730C>A		intron_variant	Intron 2 of 9	5		ENSP00000491129.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85113 AN: 151848 Hom.: 26270 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.561 AC: 85223 AN: 151966 Hom.: 26321 Cov.: 32 AF XY: 0.560 AC XY: 41600 AN XY: 74258

African (AFR) AF: 0.829 AC: 34383 AN: 41490

American (AMR) AF: 0.601 AC: 9166 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1664 AN: 3464

East Asian (EAS) AF: 0.540 AC: 2784 AN: 5160

South Asian (SAS) AF: 0.553 AC: 2665 AN: 4816

European-Finnish (FIN) AF: 0.377 AC: 3968 AN: 10538

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 28988 AN: 67924

Other (OTH) AF: 0.522 AC: 1103 AN: 2112

Alfa AF: 0.465 Hom.: 26865

Bravo AF: 0.589

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.20
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: rs10808755; hg19: chr8-68516681;