rs236394

chr6-36808967-T-Achr6-36808967-T-G

Variant summary

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

The NM_020939.2(CPNE5):c.184-8897A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,014 control chromosomes in the GnomAD database, including 24,079 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 0.55 (24079 hom., cov: 31)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2	c.184-8897A>T		intron_variant		ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7	c.184-8897A>T		intron_variant		1	NM_020939.2	A1
CPNE5	ENST00000633136.2	c.184-8897A>T		intron_variant		5		P3
CPNE5	ENST00000633280.1	c.184-8897A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83396 AN: 151896 Hom.: 24050 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.549 AC: 83471 AN: 152014 Hom.: 24079 Cov.: 31 AF XY: 0.543 AC XY: 40351 AN XY: 74298

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.528

Alfa AF: 0.376 Hom.: 994

Bravo AF: 0.574

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.0
Dann	Benign	0.82

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: rs236394; hg19: chr6-36776743;