rs864324

chr12-38729051-G-A

Variant summary

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

The NM_153634.3(CPNE8):c.798+1232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,808 control chromosomes in the GnomAD database, including 20,283 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 0.51 (20283 hom., cov: 31)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE8	NM_153634.3	c.798+1232C>T		intron_variant		ENST00000331366.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE8	ENST00000331366.10	c.798+1232C>T		intron_variant		1	NM_153634.3	P1
CPNE8	ENST00000360449.3	c.762+1232C>T		intron_variant		2
CPNE8	ENST00000551855.1	n.306+1232C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77778 AN: 151690 Hom.: 20281 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.513 AC: 77813 AN: 151808 Hom.: 20283 Cov.: 31 AF XY: 0.514 AC XY: 38132 AN XY: 74218

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.547

Alfa AF: 0.535 Hom.: 5172

Bravo AF: 0.510

Asia WGS AF: 0.544 AC: 1890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.88
Dann	Benign	0.42

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: rs864324; hg19: chr12-39122853;