rs10512839

Variant names:

• chr3-132011398-G-A
• rs10512839
• NM_130808.3:c.-2+23169C>T

Variant summary

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

The NM_130808.3(CPNE4):​c.-2+23169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,080 control chromosomes in the GnomAD database, including 32,988 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 0.65 (32988 hom., cov: 32)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 6 publications found

Genes affected

CPNE4 (HGNC:2317): (copine 4) This gene belongs to the highly conserved copine family. It encodes a calcium-dependent, phospholipid-binding protein, which may be involved in membrane trafficking, mitogenesis and development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.-2+23169C>T		intron_variant	Intron 1 of 15	ENST00000429747.6	NP_570720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE4	ENST00000429747.6	c.-2+23169C>T		intron_variant	Intron 1 of 15	1	NM_130808.3	ENSP00000411904.1
CPNE4	ENST00000511604.5	c.-2+23169C>T		intron_variant	Intron 4 of 18	1		ENSP00000423811.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98814 AN: 151960 Hom.: 32972 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.650 AC: 98858 AN: 152080 Hom.: 32988 Cov.: 32 AF XY: 0.644 AC XY: 47849 AN XY: 74334

African (AFR) AF: 0.622 AC: 25770 AN: 41464

American (AMR) AF: 0.477 AC: 7293 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2754 AN: 3468

East Asian (EAS) AF: 0.345 AC: 1780 AN: 5154

South Asian (SAS) AF: 0.743 AC: 3585 AN: 4826

European-Finnish (FIN) AF: 0.646 AC: 6834 AN: 10580

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48661 AN: 67988

Other (OTH) AF: 0.635 AC: 1341 AN: 2112

Alfa AF: 0.691 Hom.: 156524

Bravo AF: 0.627

Asia WGS AF: 0.577 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.74
PhyloP100		-0.032
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: rs10512839; hg19: chr3-131730242; COSMIC: COSV70192251;