rs10506131

chr12-38882783-A-G

Variant summary

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

The NM_153634.3(CPNE8):c.99-8272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 152,186 control chromosomes in the GnomAD database, including 298 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 0.040 (298 hom., cov: 32)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE8	NM_153634.3	c.99-8272T>C		intron_variant		ENST00000331366.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE8	ENST00000331366.10	c.99-8272T>C		intron_variant		1	NM_153634.3	P1
CPNE8	ENST00000360449.3	c.63-8272T>C		intron_variant		2
CPNE8	ENST00000550863.1	c.-385-8272T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6122 AN: 152068 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0403 AC: 6138 AN: 152186 Hom.: 298 Cov.: 32 AF XY: 0.0404 AC XY: 3010 AN XY: 74424

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0155 Hom.: 76

Bravo AF: 0.0426

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.79

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: rs10506131; hg19: chr12-39276585;