rs10512813

Variant names:

• chr3-131656480-G-C
• rs10512813
• NM_130808.3:c.681+13195C>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.681+13195C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,126 control chromosomes in the GnomAD database, including 1,098 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 0.083 (1098 hom., cov: 32)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.681+13195C>G		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.681+13195C>G		intron_variant	Intron 7 of 15	1	NM_130808.3	ENSP00000411904.1
CPNE4	ENST00000511604.5	c.681+13195C>G		intron_variant	Intron 10 of 18	1		ENSP00000423811.1

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12663 AN: 152008 Hom.: 1092 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.0340

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0901

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

GnomAD4 genome AF: 0.0834 AC: 12683 AN: 152126 Hom.: 1098 Cov.: 32 AF XY: 0.0829 AC XY: 6167 AN XY: 74378

African (AFR) AF: 0.219 AC: 9097 AN: 41460

American (AMR) AF: 0.0600 AC: 918 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5172

South Asian (SAS) AF: 0.0822 AC: 396 AN: 4818

European-Finnish (FIN) AF: 0.00377 AC: 40 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0231 AC: 1572 AN: 68002

Other (OTH) AF: 0.0935 AC: 197 AN: 2108

Alfa AF: 0.0564 Hom.: 76

Bravo AF: 0.0932

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	13
DANN	Benign	0.60
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: rs10512813; hg19: chr3-131375324;