rs10506131

Variant names:

• chr12-38882783-A-G
• rs10506131
• NM_153634.3:c.99-8272T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153634.3(CPNE8):​c.99-8272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 152,186 control chromosomes in the GnomAD database, including 298 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 0.040 (298 hom., cov: 32)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	NM_153634.3	MANE Select	c.99-8272T>C		intron	N/A	NP_705898.1	Q86YQ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	ENST00000331366.10	TSL:1 MANE Select	c.99-8272T>C		intron	N/A	ENSP00000329748.5	Q86YQ8-1
	CPNE8	ENST00000360449.3	TSL:2	c.63-8272T>C		intron	N/A	ENSP00000353633.3	E7ENV7
	CPNE8	ENST00000862791.1		c.99-8272T>C		intron	N/A	ENSP00000532850.1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6122 AN: 152068 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0403 AC: 6138 AN: 152186 Hom.: 298 Cov.: 32 AF XY: 0.0404 AC XY: 3010 AN XY: 74424

African (AFR) AF: 0.112 AC: 4652 AN: 41514

American (AMR) AF: 0.0224 AC: 343 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4818

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10590

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 755 AN: 67998

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0220 Hom.: 275

Bravo AF: 0.0426

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-0.054
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10506131;

hg19: chr12-39276585;