12-38859306-C-T

Variant names:

• chr12-38859306-C-T
• rs11169838
• NM_153634.3:c.187-10644G>A

Variant summary

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

The NM_153634.3(CPNE8):​c.187-10644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,756 control chromosomes in the GnomAD database, including 4,103 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 0.21 (4103 hom., cov: 32)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.187-10644G>A		intron_variant	Intron 3 of 19	ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.187-10644G>A		intron_variant	Intron 3 of 19	1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.151-10644G>A		intron_variant	Intron 3 of 19	2		ENSP00000353633.3
CPNE8	ENST00000550863.1	c.-297-10644G>A		intron_variant	Intron 3 of 7	4		ENSP00000447761.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31233 AN: 151640 Hom.: 4103 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.206 AC: 31233 AN: 151756 Hom.: 4103 Cov.: 32 AF XY: 0.202 AC XY: 14978 AN XY: 74152

African (AFR) AF: 0.0545 AC: 2256 AN: 41406

American (AMR) AF: 0.182 AC: 2777 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3466

East Asian (EAS) AF: 0.0513 AC: 265 AN: 5168

South Asian (SAS) AF: 0.180 AC: 864 AN: 4806

European-Finnish (FIN) AF: 0.262 AC: 2728 AN: 10430

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20581 AN: 67894

Other (OTH) AF: 0.214 AC: 451 AN: 2108

Alfa AF: 0.187 Hom.: 1544

Bravo AF: 0.191

Asia WGS AF: 0.101 AC: 352 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.48
PhyloP100		0.30
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: rs11169838; hg19: chr12-39253108;