6-36824281-C-T

Position:

• chr6-36824281-C-T

Variant summary

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

The NM_020939.2(CPNE5):​c.96-1183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,108 control chromosomes in the GnomAD database, including 7,668 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 0.31 (7668 hom., cov: 32)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848

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]

CPNE5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE5	NM_020939.2	c.96-1183G>A		intron_variant		ENST00000244751.7	NP_065990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7	c.96-1183G>A		intron_variant		1	NM_020939.2	ENSP00000244751.2
CPNE5	ENST00000633136.2	c.96-1183G>A		intron_variant		5		ENSP00000487872.2
CPNE5	ENST00000633280.1	c.96-1183G>A		intron_variant		5		ENSP00000488125.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46822 AN: 151990 Hom.: 7649 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.308 AC: 46896 AN: 152108 Hom.: 7668 Cov.: 32 AF XY: 0.313 AC XY: 23307 AN XY: 74360

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.317

Alfa AF: 0.267 Hom.: 1972

Bravo AF: 0.309

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.71

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: rs236373; hg19: chr6-36792057;