rs17126713

Variant names:

• chr12-38825216-G-A
• rs17126713
• NM_153634.3:c.407+4163C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153634.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	NM_153634.3	MANE Select	c.407+4163C>T		intron	N/A	NP_705898.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	ENST00000331366.10	TSL:1 MANE Select	c.407+4163C>T		intron	N/A	ENSP00000329748.5
	CPNE8	ENST00000360449.3	TSL:2	c.371+4163C>T		intron	N/A	ENSP00000353633.3
	CPNE8	ENST00000550863.1	TSL:4	c.-77+4163C>T		intron	N/A	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

African (AFR) AF: 0.107 AC: 4444 AN: 41522

American (AMR) AF: 0.0551 AC: 843 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 239 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1448 AN: 5156

South Asian (SAS) AF: 0.0854 AC: 412 AN: 4826

European-Finnish (FIN) AF: 0.0359 AC: 380 AN: 10596

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0616 AC: 4192 AN: 67998

Other (OTH) AF: 0.0794 AC: 168 AN: 2116

Alfa AF: 0.0684 Hom.: 177

Bravo AF: 0.0833

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.4
DANN	Benign	0.81
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17126713; hg19: chr12-39219018;