NM_130808.3:c.-2+1636T>G

Variant names:

• chr3-132032931-A-C
• rs13076253
• NM_130808.3:c.-2+1636T>G

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+1636T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,272 control chromosomes in the GnomAD database, including 1,794 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 0.15 (1794 hom., cov: 34)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.-2+1636T>G		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+1636T>G		intron_variant	Intron 1 of 15	1	NM_130808.3	ENSP00000411904.1
CPNE4	ENST00000511604.5	c.-2+1636T>G		intron_variant	Intron 4 of 18	1		ENSP00000423811.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23212 AN: 152154 Hom.: 1793 Cov.: 34

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.153 AC: 23225 AN: 152272 Hom.: 1794 Cov.: 34 AF XY: 0.153 AC XY: 11391 AN XY: 74456

African (AFR) AF: 0.181 AC: 7519 AN: 41546

American (AMR) AF: 0.108 AC: 1648 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.118 AC: 611 AN: 5180

South Asian (SAS) AF: 0.131 AC: 631 AN: 4826

European-Finnish (FIN) AF: 0.189 AC: 2000 AN: 10602

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9607 AN: 68026

Other (OTH) AF: 0.167 AC: 353 AN: 2112

Alfa AF: 0.142 Hom.: 6461

Bravo AF: 0.147

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		0.066
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: rs13076253; hg19: chr3-131751775;