8-67509330-A-G

Position:

• chr8-67509330-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020361.5(CPA6):​c.534+187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,066 control chromosomes in the GnomAD database, including 17,601 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 (17601 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA6	NM_020361.5	c.534+187T>C		intron_variant		ENST00000297770.10
CPA6	XM_017013646.2	c.90+187T>C		intron_variant
CPA6	XM_017013647.2	c.534+187T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA6	ENST00000297770.10	c.534+187T>C		intron_variant		1	NM_020361.5	P1
CPA6	ENST00000479862.6	c.*130+187T>C		intron_variant, NMD_transcript_variant		1
CPA6	ENST00000518549.1	n.748+187T>C		intron_variant, non_coding_transcript_variant		1
CPA6	ENST00000638254.1	c.*130+187T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69617 AN: 151944 Hom.: 17563 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.458 AC: 69697 AN: 152066 Hom.: 17601 Cov.: 32 AF XY: 0.454 AC XY: 33750 AN XY: 74340

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.448

Alfa AF: 0.401 Hom.: 1655

Bravo AF: 0.475

Asia WGS AF: 0.337 AC: 1170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1393902; hg19: chr8-68421565;