6-36787443-A-G

Position:

• chr6-36787443-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.528+4590T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,556 control chromosomes in the GnomAD database, including 7,609 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 0.30 (7609 hom., cov: 30)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2	c.528+4590T>C		intron_variant		ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7	c.528+4590T>C		intron_variant		1	NM_020939.2	A1
CPNE5	ENST00000633136.2	c.579+4590T>C		intron_variant		5		P3
CPNE5	ENST00000633280.1	c.576+4590T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45676 AN: 151438 Hom.: 7588 Cov.: 30

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.302 AC: 45726 AN: 151556 Hom.: 7609 Cov.: 30 AF XY: 0.301 AC XY: 22291 AN XY: 74038

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.314

Alfa AF: 0.263 Hom.: 6040

Bravo AF: 0.325

Asia WGS AF: 0.301 AC: 1046 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	6.8
DANN	Benign	0.78

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: rs236411; hg19: chr6-36755220;