rs10456444

chr6-36755065-T-C

Variant summary

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

The NM_020939.2(CPNE5):c.909+1180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,132 control chromosomes in the GnomAD database, including 14,960 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 0.44 (14958 hom., cov: 33)
  • Exomes 𝑓: 0.58 (2 hom.)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2	c.909+1180A>G		intron_variant		ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7	c.909+1180A>G		intron_variant		1	NM_020939.2	A1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66980 AN: 152004 Hom.: 14955 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.583 AC: 7 AN: 12 Hom.: 2 Cov.: 0 AF XY: 0.625 AC XY: 5 AN XY: 8

Gnomad4 NFE exome AF: 0.583

GnomAD4 genome AF: 0.440 AC: 67001 AN: 152120 Hom.: 14958 Cov.: 33 AF XY: 0.433 AC XY: 32215 AN XY: 74374

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.447

Alfa AF: 0.465 Hom.: 24539

Bravo AF: 0.441

Asia WGS AF: 0.347 AC: 1205 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.1
Dann	Benign	0.86

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: rs10456444; hg19: chr6-36722842;