rs1393902

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-67509330-A-C
• chr8-67509330-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020361.5(CPA6):​c.534+187T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA6	NM_020361.5	c.534+187T>G		intron_variant	Intron 5 of 10	ENST00000297770.10	NP_065094.3
CPA6	NM_001440615.1	c.534+187T>G		intron_variant	Intron 5 of 6		NP_001427544.1
CPA6	XM_017013646.2	c.90+187T>G		intron_variant	Intron 5 of 10		XP_016869135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA6	ENST00000297770.10	c.534+187T>G		intron_variant	Intron 5 of 10	1	NM_020361.5	ENSP00000297770.4
CPA6	ENST00000479862.6	n.*130+187T>G		intron_variant	Intron 4 of 7	1		ENSP00000419016.2
CPA6	ENST00000518549.1	n.748+187T>G		intron_variant	Intron 5 of 7	1
CPA6	ENST00000638254.1	n.*130+187T>G		intron_variant	Intron 4 of 9	5		ENSP00000491129.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.54
PhyloP100		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;