12-38848667-GGAAA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_153634.3(CPNE8):c.187-9_187-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,580,714 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: CPNE8 NM_153634.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.26

Genes affected

CPNE8 (HGNC:23498): (copine 8) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-38848667-GGAAA-G is Benign according to our data. Variant chr12-38848667-GGAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642846.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE8	NM_153634.3	c.187-9_187-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000331366.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE8	ENST00000331366.10	c.187-9_187-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_153634.3	P1
CPNE8	ENST00000360449.3	c.151-9_151-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
CPNE8	ENST00000550863.1	c.-297-9_-297-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00203 AC: 309 AN: 152084 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000516 AC: 113 AN: 219028 Hom.: 1 AF XY: 0.000378 AC XY: 45 AN XY: 119072

Gnomad AFR exome AF: 0.00719

Gnomad AMR exome AF: 0.000268

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000194

Gnomad OTH exome AF: 0.000569

GnomAD4 exome AF: 0.000207 AC: 296 AN: 1428512 Hom.: 0 AF XY: 0.000183 AC XY: 130 AN XY: 710018

Gnomad4 AFR exome AF: 0.00724

Gnomad4 AMR exome AF: 0.000302

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000173

Gnomad4 OTH exome AF: 0.000594

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152202 Hom.: 2 Cov.: 32 AF XY: 0.00202 AC XY: 150 AN XY: 74412

Gnomad4 AFR AF: 0.00715

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00113 Hom.: 0

Bravo AF: 0.00247

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CPNE8: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs571596831; hg19: chr12-39242469;