20-35633233-G-T

Variant names:

• chr20-35633233-G-T
• rs6060524
• NM_152925.3:c.1-310C>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.1-310C>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 152,206 control chromosomes in the GnomAD database, including 824 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 (824 hom., cov: 31)
• Consequence: CPNE1 NM_152925.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 19 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE1	NM_152925.3	c.1-310C>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.1-310C>A		intron_variant	Intron 1 of 15	5	NM_152925.3	ENSP00000380585.1
CPNE1	ENST00000437340.5	c.1-310C>A		intron_variant	Intron 1 of 15	1		ENSP00000415597.1
ENSG00000272897	ENST00000541176.2	n.*33-310C>A		intron_variant	Intron 6 of 8	2		ENSP00000443983.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15458 AN: 152088 Hom.: 823 Cov.: 31

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.102 AC: 15465 AN: 152206 Hom.: 824 Cov.: 31 AF XY: 0.100 AC XY: 7466 AN XY: 74428

African (AFR) AF: 0.0948 AC: 3934 AN: 41498

American (AMR) AF: 0.108 AC: 1656 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.0767 AC: 397 AN: 5178

South Asian (SAS) AF: 0.145 AC: 696 AN: 4814

European-Finnish (FIN) AF: 0.0817 AC: 867 AN: 10614

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7128 AN: 68020

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.0894 Hom.: 451

Bravo AF: 0.102

Asia WGS AF: 0.144 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.72
PhyloP100		-0.22
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: rs6060524; hg19: chr20-34221155;