8-86544925-C-T

Variant names:

• chr8-86544925-C-T
• rs17609515
• NM_003909.5:c.732+87C>T

Variant summary

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

The NM_003909.5(CPNE3):​c.732+87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 676,220 control chromosomes in the GnomAD database, including 1,943 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 0.054 (315 hom., cov: 32)
  • Exomes 𝑓: 0.072 (1628 hom.)
• Consequence: CPNE3 NM_003909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 3 publications found

Genes affected

CPNE3 (HGNC:2316): (copine 3) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a protein which contains two type II C2 domains in the amino-terminus and an A domain-like sequence in the carboxy-terminus. The A domain mediates interactions between integrins and extracellular ligands. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003909.5. 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
	CPNE3	NM_003909.5	MANE Select	c.732+87C>T		intron	N/A	NP_003900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE3	ENST00000517490.6	TSL:1 MANE Select	c.732+87C>T		intron	N/A	ENSP00000477590.1
	CPNE3	ENST00000517862.1	TSL:3	n.246C>T		non_coding_transcript_exon	Exon 2 of 2
	CPNE3	ENST00000517391.5	TSL:3	c.396+87C>T		intron	N/A	ENSP00000428561.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8270 AN: 152046 Hom.: 316 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.0570

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0721 AC: 37795 AN: 524056 Hom.: 1628 Cov.: 7 AF XY: 0.0711 AC XY: 20061 AN XY: 282008

African (AFR) AF: 0.0141 AC: 171 AN: 12086

American (AMR) AF: 0.0354 AC: 768 AN: 21714

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 1311 AN: 13224

East Asian (EAS) AF: 0.0000362 AC: 1 AN: 27618

South Asian (SAS) AF: 0.0140 AC: 487 AN: 34814

European-Finnish (FIN) AF: 0.0583 AC: 2008 AN: 34436

Middle Eastern (MID) AF: 0.0267 AC: 92 AN: 3446

European-Non Finnish (NFE) AF: 0.0890 AC: 31184 AN: 350416

Other (OTH) AF: 0.0674 AC: 1773 AN: 26302

GnomAD4 genome AF: 0.0543 AC: 8269 AN: 152164 Hom.: 315 Cov.: 32 AF XY: 0.0512 AC XY: 3805 AN XY: 74374

African (AFR) AF: 0.0141 AC: 584 AN: 41534

American (AMR) AF: 0.0444 AC: 678 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4824

European-Finnish (FIN) AF: 0.0570 AC: 602 AN: 10570

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0867 AC: 5898 AN: 67994

Other (OTH) AF: 0.0559 AC: 118 AN: 2112

Alfa AF: 0.0454 Hom.: 34

Bravo AF: 0.0529

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.73
PhyloP100		-1.6
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: rs17609515; hg19: chr8-87557153;