6-36779629-C-T

Variant names:

• chr6-36779629-C-T
• rs4714010
• NM_020939.2:c.529-672G>A

Variant summary

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

The NM_020939.2(CPNE5):​c.529-672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,032 control chromosomes in the GnomAD database, including 12,240 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 0.40 (12240 hom., cov: 32)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE5	NM_020939.2	c.529-672G>A		intron_variant	Intron 8 of 20	ENST00000244751.7	NP_065990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7	c.529-672G>A		intron_variant	Intron 8 of 20	1	NM_020939.2	ENSP00000244751.2
CPNE5	ENST00000633136.2	c.580-672G>A		intron_variant	Intron 9 of 21	5		ENSP00000487872.2
CPNE5	ENST00000633280.1	c.577-672G>A		intron_variant	Intron 9 of 9	5		ENSP00000488125.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60454 AN: 151914 Hom.: 12229 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.398 AC: 60510 AN: 152032 Hom.: 12240 Cov.: 32 AF XY: 0.394 AC XY: 29316 AN XY: 74312

African (AFR) AF: 0.380 AC: 15757 AN: 41462

American (AMR) AF: 0.380 AC: 5805 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1593 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1069 AN: 5172

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4814

European-Finnish (FIN) AF: 0.439 AC: 4639 AN: 10562

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29264 AN: 67954

Other (OTH) AF: 0.392 AC: 827 AN: 2110

Alfa AF: 0.410 Hom.: 27989

Bravo AF: 0.396

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.74
PhyloP100		0.046
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4714010; hg19: chr6-36747406;