NM_130808.3:c.-1-1871G>A

Variant names:

• chr3-131907315-C-T
• rs1225006
• NM_130808.3:c.-1-1871G>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.-1-1871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,986 control chromosomes in the GnomAD database, including 38,806 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 0.71 (38806 hom., cov: 31)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.-1-1871G>A		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.-1-1871G>A		intron_variant	Intron 1 of 15	1	NM_130808.3	ENSP00000411904.1
CPNE4	ENST00000511604.5	c.-1-1871G>A		intron_variant	Intron 4 of 18	1		ENSP00000423811.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108098 AN: 151868 Hom.: 38778 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.712 AC: 108175 AN: 151986 Hom.: 38806 Cov.: 31 AF XY: 0.711 AC XY: 52827 AN XY: 74272

African (AFR) AF: 0.671 AC: 27793 AN: 41428

American (AMR) AF: 0.806 AC: 12297 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2492 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4004 AN: 5148

South Asian (SAS) AF: 0.627 AC: 3017 AN: 4814

European-Finnish (FIN) AF: 0.732 AC: 7752 AN: 10590

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48383 AN: 67958

Other (OTH) AF: 0.737 AC: 1557 AN: 2114

Alfa AF: 0.704 Hom.: 10324

Bravo AF: 0.718

Asia WGS AF: 0.664 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
DANN	Benign	0.46
PhyloP100		-0.35
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: rs1225006; hg19: chr3-131626159;