rs826838

Positions:

• chr12-38712929-C-T

Variant summary

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

The NM_153634.3(CPNE8):​c.915-10008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,924 control chromosomes in the GnomAD database, including 21,428 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 0.52 (21428 hom., cov: 32)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.915-10008G>A		intron_variant		ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.915-10008G>A		intron_variant		1	NM_153634.3	ENSP00000329748	P1
CPNE8	ENST00000538596.6	c.-80+7724G>A		intron_variant		1		ENSP00000439237
CPNE8	ENST00000360449.3	c.879-10008G>A		intron_variant		2		ENSP00000353633

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78544 AN: 151806 Hom.: 21430 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.517 AC: 78562 AN: 151924 Hom.: 21428 Cov.: 32 AF XY: 0.521 AC XY: 38677 AN XY: 74252

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.563

Alfa AF: 0.558 Hom.: 7747

Bravo AF: 0.512

Asia WGS AF: 0.712 AC: 2476 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	0.16
DANN	Benign	0.27

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: rs826838; hg19: chr12-39106731;