rs9470387

chr6-36746081-C-A

Variant summary

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

The NM_020939.2(CPNE5):c.1200+315G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 797,838 control chromosomes in the GnomAD database, including 39,644 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 0.27 (5735 hom., cov: 32)
  • Exomes 𝑓: 0.32 (33909 hom.)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

Genes affected

CPNE5 (HGNC:2318): (copine 5) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2	c.1200+315G>T		intron_variant		ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7	c.1200+315G>T		intron_variant		1	NM_020939.2	A1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41068 AN: 151902 Hom.: 5736 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.322 AC: 207982 AN: 645818 Hom.: 33909 AF XY: 0.321 AC XY: 96751 AN XY: 301702

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.270 AC: 41095 AN: 152020 Hom.: 5735 Cov.: 32 AF XY: 0.264 AC XY: 19614 AN XY: 74304

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.246

Alfa AF: 0.301 Hom.: 11791

Bravo AF: 0.262

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.6
Dann	Benign	0.88

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: rs9470387; hg19: chr6-36713858;