rs1393901

chr8-67513099-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA6	NM_020361.5	c.318-1444A>G		intron_variant		ENST00000297770.10
CPA6	XM_017013646.2	c.-127-1444A>G		intron_variant
CPA6	XM_017013647.2	c.318-1444A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA6	ENST00000297770.10	c.318-1444A>G		intron_variant		1	NM_020361.5	P1
CPA6	ENST00000479862.6	c.193-1444A>G		intron_variant, NMD_transcript_variant		1
CPA6	ENST00000518549.1	n.532-1444A>G		intron_variant, non_coding_transcript_variant		1
CPA6	ENST00000638254.1	c.193-1444A>G		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.447

Alfa AF: 0.385 Hom.: 4633

Bravo AF: 0.472

Asia WGS AF: 0.336 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.4
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs1393901; hg19: chr8-68425334; COSMIC: COSV52740921;