rs7308580

chr12-38891156-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.98+14281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 151,956 control chromosomes in the GnomAD database, including 170 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 0.044 (170 hom., cov: 31)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE8	NM_153634.3	c.98+14281G>A		intron_variant		ENST00000331366.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE8	ENST00000331366.10	c.98+14281G>A		intron_variant		1	NM_153634.3	P1
CPNE8	ENST00000360449.3	c.62+16163G>A		intron_variant		2
CPNE8	ENST00000550863.1	c.-386+14986G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6624 AN: 151838 Hom.: 170 Cov.: 31

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0462

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

GnomAD4 genome AF: 0.0436 AC: 6623 AN: 151956 Hom.: 170 Cov.: 31 AF XY: 0.0431 AC XY: 3200 AN XY: 74242

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0332

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.0452

Alfa AF: 0.0452 Hom.: 26

Bravo AF: 0.0423

Asia WGS AF: 0.0930 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.62

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: rs7308580; hg19: chr12-39284958;