12-38737190-T-C

Position:

• chr12-38737190-T-C

Variant summary

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

The NM_153634.3(CPNE8):​c.723-6832A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,394 control chromosomes in the GnomAD database, including 23,671 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 0.55 (23671 hom., cov: 31)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.723-6832A>G		intron_variant		ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.723-6832A>G		intron_variant		1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.687-6832A>G		intron_variant		2		ENSP00000353633.3
CPNE8	ENST00000551855.1	n.231-6832A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83653 AN: 151314 Hom.: 23674 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.553 AC: 83665 AN: 151394 Hom.: 23671 Cov.: 31 AF XY: 0.555 AC XY: 41008 AN XY: 73934

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.588

Alfa AF: 0.428 Hom.: 1139

Bravo AF: 0.551

Asia WGS AF: 0.712 AC: 2466 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.55

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: rs1352123; hg19: chr12-39130992;