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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.99-8272T>C		intron_variant	Intron 1 of 19	ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.99-8272T>C		intron_variant	Intron 1 of 19	1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.63-8272T>C		intron_variant	Intron 1 of 19	2		ENSP00000353633.3
CPNE8	ENST00000550863.1	c.-385-8272T>C		intron_variant	Intron 1 of 7	4		ENSP00000447761.1

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 v4.3

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

Other links and lift over

dbSNP: rs10506131; hg19: chr12-39276585;