6-36765293-A-G

Position:

• chr6-36765293-A-G

Variant summary

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

The NM_020939.2(CPNE5):​c.779+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,605,494 control chromosomes in the GnomAD database, including 11,428 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 0.14 (1477 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9951 hom.)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2	c.779+42T>C		intron_variant		ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7	c.779+42T>C		intron_variant		1	NM_020939.2	A1
CPNE5	ENST00000633136.2	c.830+42T>C		intron_variant		5		P3

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20722 AN: 151190 Hom.: 1480 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.131

GnomAD3 exomes AF: 0.124 AC: 30593 AN: 247064 Hom.: 2037 AF XY: 0.123 AC XY: 16492 AN XY: 133556

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0892

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.114 AC: 166253 AN: 1454186 Hom.: 9951 Cov.: 29 AF XY: 0.115 AC XY: 82981 AN XY: 723638

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0911

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.137 AC: 20731 AN: 151308 Hom.: 1477 Cov.: 32 AF XY: 0.138 AC XY: 10210 AN XY: 73936

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.131

Alfa AF: 0.120 Hom.: 1945

Bravo AF: 0.135

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.68

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: rs3752482; hg19: chr6-36733070; COSMIC: COSV55195434;