NM_020939.2:c.1564-6T>C

Variant names:

• chr6-36742492-A-G
• rs3752480
• NM_020939.2:c.1564-6T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020939.2(CPNE5):​c.1564-6T>C variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.0003679
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020939.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE5	NM_020939.2	MANE Select	c.1564-6T>C		splice_region intron	N/A	NP_065990.1
	CPNE5	NM_001410887.1		c.1615-6T>C		splice_region intron	N/A	NP_001397816.1
	CPNE5	NM_001376889.1		c.1615-742T>C		intron	N/A	NP_001363818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE5	ENST00000244751.7	TSL:1 MANE Select	c.1564-6T>C		splice_region intron	N/A	ENSP00000244751.2
	CPNE5	ENST00000393189.2	TSL:1	c.688-6T>C		splice_region intron	N/A	ENSP00000376885.2
	CPNE5	ENST00000493411.2	TSL:1	n.744-6T>C		splice_region intron	N/A

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

GnomAD2 exomes AF: 0.195 AC: 48092 AN: 246112 AF XY: 0.198

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 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

African (AFR) AF: 0.0597 AC: 1994 AN: 33414

American (AMR) AF: 0.195 AC: 8723 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4725 AN: 26064

East Asian (EAS) AF: 0.284 AC: 11249 AN: 39600

South Asian (SAS) AF: 0.213 AC: 18345 AN: 86182

European-Finnish (FIN) AF: 0.173 AC: 8651 AN: 49942

Middle Eastern (MID) AF: 0.179 AC: 1029 AN: 5756

European-Non Finnish (NFE) AF: 0.199 AC: 220296 AN: 1109516

Other (OTH) AF: 0.193 AC: 11635 AN: 60188

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

African (AFR) AF: 0.0641 AC: 2662 AN: 41498

American (AMR) AF: 0.201 AC: 3072 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3468

East Asian (EAS) AF: 0.267 AC: 1374 AN: 5152

South Asian (SAS) AF: 0.212 AC: 1025 AN: 4828

European-Finnish (FIN) AF: 0.176 AC: 1864 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13965 AN: 67930

Other (OTH) AF: 0.170 AC: 359 AN: 2112

Alfa AF: 0.191 Hom.: 9915

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.51
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3752480; hg19: chr6-36710269; COSMIC: COSV55196720; COSMIC: COSV55196720;