rs12632185

Variant names:

• chr3-131602478-C-T
• rs12632185
• NM_130808.3:c.682-14896G>A

Variant summary

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

The NM_130808.3(CPNE4):​c.682-14896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,024 control chromosomes in the GnomAD database, including 11,414 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 0.31 (11414 hom., cov: 32)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.682-14896G>A		intron_variant	Intron 7 of 15	ENST00000429747.6	NP_570720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE4	ENST00000429747.6	c.682-14896G>A		intron_variant	Intron 7 of 15	1	NM_130808.3	ENSP00000411904.1
CPNE4	ENST00000511604.5	c.682-14896G>A		intron_variant	Intron 10 of 18	1		ENSP00000423811.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46479 AN: 151906 Hom.: 11369 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.306 AC: 46577 AN: 152024 Hom.: 11414 Cov.: 32 AF XY: 0.301 AC XY: 22356 AN XY: 74300

African (AFR) AF: 0.686 AC: 28416 AN: 41438

American (AMR) AF: 0.194 AC: 2969 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3466

East Asian (EAS) AF: 0.175 AC: 900 AN: 5156

South Asian (SAS) AF: 0.224 AC: 1077 AN: 4812

European-Finnish (FIN) AF: 0.137 AC: 1455 AN: 10584

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10021 AN: 67972

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.199 Hom.: 6428

Bravo AF: 0.326

Asia WGS AF: 0.261 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.56
PhyloP100		1.0
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: rs12632185; hg19: chr3-131321322;