NM_152925.3:c.1-14677G>A

Variant names:

• chr20-35647600-C-T
• rs6060535
• NM_152925.3:c.1-14677G>A

Variant summary

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

The NM_152925.3(CPNE1):​c.1-14677G>A 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 151,952 control chromosomes in the GnomAD database, including 827 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 (827 hom., cov: 30)
• Consequence: CPNE1 NM_152925.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 15 publications found

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:):

RNU6-759P (HGNC:47722): (RNA, U6 small nuclear 759, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• 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 rank	MANE	Protein	UniProt
CPNE1	NM_152925.3	c.1-14677G>A		intron_variant	Intron 1 of 15	ENST00000397443.7	NP_690902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE1	ENST00000397443.7	c.1-14677G>A		intron_variant	Intron 1 of 15	5	NM_152925.3	ENSP00000380585.1
CPNE1	ENST00000437340.5	c.1-14677G>A		intron_variant	Intron 1 of 15	1		ENSP00000415597.1
ENSG00000272897	ENST00000541176.2	n.*32+7602G>A		intron_variant	Intron 6 of 8	2		ENSP00000443983.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15491 AN: 151834 Hom.: 826 Cov.: 30

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.137

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: 15498 AN: 151952 Hom.: 827 Cov.: 30 AF XY: 0.101 AC XY: 7480 AN XY: 74264

African (AFR) AF: 0.0950 AC: 3934 AN: 41424

American (AMR) AF: 0.108 AC: 1645 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3468

East Asian (EAS) AF: 0.0794 AC: 409 AN: 5152

South Asian (SAS) AF: 0.146 AC: 701 AN: 4802

European-Finnish (FIN) AF: 0.0828 AC: 873 AN: 10548

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7135 AN: 67994

Other (OTH) AF: 0.115 AC: 241 AN: 2104

Alfa AF: 0.104 Hom.: 527

Bravo AF: 0.102

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		-0.20
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: rs6060535; hg19: chr20-34235522;