12-38849391-C-G

Position:

• chr12-38849391-C-G

Variant summary

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

The NM_153634.3(CPNE8):​c.187-729G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,166 control chromosomes in the GnomAD database, including 2,402 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 0.14 (2402 hom., cov: 32)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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]

CPNE8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.187-729G>C		intron_variant		ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.187-729G>C		intron_variant		1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.151-729G>C		intron_variant		2		ENSP00000353633.3
CPNE8	ENST00000550863.1	c.-297-729G>C		intron_variant		4		ENSP00000447761.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21182 AN: 152048 Hom.: 2398 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0625

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.139 AC: 21221 AN: 152166 Hom.: 2402 Cov.: 32 AF XY: 0.136 AC XY: 10119 AN XY: 74402

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.0856

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.0625

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0992 Hom.: 154

Bravo AF: 0.151

Asia WGS AF: 0.175 AC: 607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.59

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: rs9943730; hg19: chr12-39243193;