rs7308580

Variant names:

• chr12-38891156-C-T
• rs7308580
• NM_153634.3:c.98+14281G>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.98+14281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 151,956 control chromosomes in the GnomAD database, including 170 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 0.044 (170 hom., cov: 31)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 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.98+14281G>A		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.98+14281G>A		intron	N/A	ENSP00000329748.5	Q86YQ8-1
	CPNE8	ENST00000360449.3	TSL:2	c.62+16163G>A		intron	N/A	ENSP00000353633.3	E7ENV7
	CPNE8	ENST00000862791.1		c.98+14281G>A		intron	N/A	ENSP00000532850.1

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6624 AN: 151838 Hom.: 170 Cov.: 31

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0462

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

GnomAD4 genome AF: 0.0436 AC: 6623 AN: 151956 Hom.: 170 Cov.: 31 AF XY: 0.0431 AC XY: 3200 AN XY: 74242

African (AFR) AF: 0.0167 AC: 693 AN: 41474

American (AMR) AF: 0.0332 AC: 506 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3470

East Asian (EAS) AF: 0.122 AC: 627 AN: 5120

South Asian (SAS) AF: 0.0675 AC: 324 AN: 4800

European-Finnish (FIN) AF: 0.0356 AC: 376 AN: 10550

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3808 AN: 67994

Other (OTH) AF: 0.0452 AC: 95 AN: 2100

Alfa AF: 0.0446 Hom.: 27

Bravo AF: 0.0423

Asia WGS AF: 0.0930 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.16
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: rs7308580;

hg19: chr12-39284958;