rs12480408

Positions:

• chr20-35646878-A-G

Variant summary

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

The NM_152925.3(CPNE1):​c.1-13955T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,250 control chromosomes in the GnomAD database, including 833 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 0.10 (833 hom., cov: 30)
• Consequence: CPNE1 NM_152925.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

Genes affected

CPNE1 (HGNC:2314): (copine 1) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]

ENSG00000272897 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE1	NM_152925.3	c.1-13955T>C		intron_variant		ENST00000397443.7	NP_690902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE1	ENST00000397443.7	c.1-13955T>C		intron_variant		5	NM_152925.3	ENSP00000380585.1
CPNE1	ENST00000437340.5	c.1-13955T>C		intron_variant		1		ENSP00000415597.1
ENSG00000272897	ENST00000541176.2	n.*32+8324T>C		intron_variant		2		ENSP00000443983.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15549 AN: 152132 Hom.: 832 Cov.: 30

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.102 AC: 15556 AN: 152250 Hom.: 833 Cov.: 30 AF XY: 0.101 AC XY: 7509 AN XY: 74450

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.114

Alfa AF: 0.104 Hom.: 258

Bravo AF: 0.102

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.73

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: rs12480408; hg19: chr20-34234800;