rs16837140

Positions:

• chr3-131571787-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130808.3(CPNE4):​c.927+3284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,912 control chromosomes in the GnomAD database, including 1,144 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 0.11 (1144 hom., cov: 32)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.927+3284G>A		intron_variant		ENST00000429747.6	NP_570720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE4	ENST00000429747.6	c.927+3284G>A		intron_variant		1	NM_130808.3	ENSP00000411904	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16631 AN: 151794 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0990

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

GnomAD4 genome AF: 0.110 AC: 16651 AN: 151912 Hom.: 1144 Cov.: 32 AF XY: 0.109 AC XY: 8098 AN XY: 74226

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0553

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0812 Hom.: 803

Bravo AF: 0.111

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs16837140; hg19: chr3-131290631;