rs12425783

Variant names:

• chr12-38856882-T-C
• rs12425783
• NM_153634.3:c.187-8220A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153634.3(CPNE8):​c.187-8220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 152,110 control chromosomes in the GnomAD database, including 635 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 0.081 (635 hom., cov: 32)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.187-8220A>G		intron_variant	Intron 3 of 19	ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.187-8220A>G		intron_variant	Intron 3 of 19	1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.151-8220A>G		intron_variant	Intron 3 of 19	2		ENSP00000353633.3
CPNE8	ENST00000550863.1	c.-297-8220A>G		intron_variant	Intron 3 of 7	4		ENSP00000447761.1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12302 AN: 151992 Hom.: 636 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0687

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0804

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

GnomAD4 genome AF: 0.0809 AC: 12310 AN: 152110 Hom.: 635 Cov.: 32 AF XY: 0.0803 AC XY: 5974 AN XY: 74364

African (AFR) AF: 0.110 AC: 4581 AN: 41498

American (AMR) AF: 0.0555 AC: 849 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0687 AC: 238 AN: 3464

East Asian (EAS) AF: 0.280 AC: 1449 AN: 5178

South Asian (SAS) AF: 0.0849 AC: 409 AN: 4820

European-Finnish (FIN) AF: 0.0358 AC: 379 AN: 10584

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

European-Non Finnish (NFE) AF: 0.0618 AC: 4196 AN: 67950

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.0640 Hom.: 257

Bravo AF: 0.0845

Asia WGS AF: 0.163 AC: 564 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.93
PhyloP100		0.31
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: rs12425783; hg19: chr12-39250684;