chr12-38729051-G-A

Variant names:

• chr12-38729051-G-A
• rs864324
• NM_153634.3:c.798+1232C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153634.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	NM_153634.3	MANE Select	c.798+1232C>T		intron	N/A	NP_705898.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	ENST00000331366.10	TSL:1 MANE Select	c.798+1232C>T		intron	N/A	ENSP00000329748.5
	CPNE8	ENST00000360449.3	TSL:2	c.762+1232C>T		intron	N/A	ENSP00000353633.3
	CPNE8	ENST00000551855.1	TSL:3	n.306+1232C>T		intron	N/A

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

African (AFR) AF: 0.439 AC: 18203 AN: 41430

American (AMR) AF: 0.550 AC: 8364 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2234 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2477 AN: 5158

South Asian (SAS) AF: 0.582 AC: 2803 AN: 4814

European-Finnish (FIN) AF: 0.475 AC: 5027 AN: 10578

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36752 AN: 67862

Other (OTH) AF: 0.547 AC: 1147 AN: 2096

Alfa AF: 0.533 Hom.: 5251

Bravo AF: 0.510

Asia WGS AF: 0.544 AC: 1890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.88
DANN	Benign	0.42
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs864324; hg19: chr12-39122853;