rs3752480

Positions:

• chr6-36742492-A-G
• chr6-36742492-A-T

Variant summary

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

The NM_020939.2(CPNE5):​c.1564-6T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,607,348 control chromosomes in the GnomAD database, including 31,702 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2395 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29307 hom.)
• Consequence: CPNE5 NM_020939.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003679
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2	c.1564-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7	c.1564-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020939.2	A1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25211 AN: 151938 Hom.: 2398 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.171

GnomAD3 exomes AF: 0.195 AC: 48092 AN: 246112 Hom.: 4956 AF XY: 0.198 AC XY: 26394 AN XY: 133358

Gnomad AFR exome AF: 0.0637

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.273

Gnomad SAS exome AF: 0.214

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.197 AC: 286647 AN: 1455292 Hom.: 29307 Cov.: 35 AF XY: 0.198 AC XY: 143503 AN XY: 723504

Gnomad4 AFR exome AF: 0.0597

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.166 AC: 25195 AN: 152056 Hom.: 2395 Cov.: 32 AF XY: 0.167 AC XY: 12425 AN XY: 74338

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.170

Alfa AF: 0.198 Hom.: 6853

Bravo AF: 0.162

Asia WGS AF: 0.194 AC: 676 AN: 3478

EpiCase AF: 0.211

EpiControl AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00037
dbscSNV1_RF	Benign	0.040
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: rs3752480; hg19: chr6-36710269; COSMIC: COSV55196720; COSMIC: COSV55196720;