rs17126713

Positions:

• chr12-38825216-G-A

Variant summary

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

The NM_153634.3(CPNE8):​c.407+4163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 152,182 control chromosomes in the GnomAD database, including 627 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 0.080 (627 hom., cov: 32)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

CPNE8 (HGNC:23498): (copine 8) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. [provided by RefSeq, Jul 2008]

CPNE8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.407+4163C>T		intron_variant		ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.407+4163C>T		intron_variant		1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.371+4163C>T		intron_variant		2		ENSP00000353633.3
CPNE8	ENST00000550863.1	c.-77+4163C>T		intron_variant		4		ENSP00000447761.1

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12162 AN: 152064 Hom.: 628 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0802

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

GnomAD4 genome AF: 0.0800 AC: 12167 AN: 152182 Hom.: 627 Cov.: 32 AF XY: 0.0794 AC XY: 5909 AN XY: 74390

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0551

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.0616

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0677 Hom.: 146

Bravo AF: 0.0833

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.4
DANN	Benign	0.81

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: rs17126713; hg19: chr12-39219018;