8-67665731-A-G

Position:

• chr8-67665731-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020361.5(CPA6):​c.117-41480T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,272 control chromosomes in the GnomAD database, including 87 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 0.030 (87 hom., cov: 32)
• Consequence: CPA6 NM_020361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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=-0.97).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0299 (4560/152272) while in subpopulation AFR AF= 0.0461 (1914/41546). AF 95% confidence interval is 0.0444. There are 87 homozygotes in gnomad4. There are 2130 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 87 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA6	NM_020361.5	c.117-41480T>C		intron_variant		ENST00000297770.10
CPA6	XM_017013646.2	c.-204+3545T>C		intron_variant
CPA6	XM_017013647.2	c.117-41480T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA6	ENST00000297770.10	c.117-41480T>C		intron_variant		1	NM_020361.5	P1
CPA6	ENST00000479862.6	c.117-41480T>C		intron_variant, NMD_transcript_variant		1
CPA6	ENST00000518549.1	n.331-41480T>C		intron_variant, non_coding_transcript_variant		1
CPA6	ENST00000638254.1	c.117-41480T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4538 AN: 152154 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0299 AC: 4560 AN: 152272 Hom.: 87 Cov.: 32 AF XY: 0.0286 AC XY: 2130 AN XY: 74468

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.0349

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00556

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0281 Hom.: 14

Bravo AF: 0.0319

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.70
DANN	Benign	0.59

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: rs6993502; hg19: chr8-68577966;