8-86544925-C-T

Position:

• chr8-86544925-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000517490.6(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 ENST00000517490.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE3	NM_003909.5	c.732+87C>T		intron_variant		ENST00000517490.6	NP_003900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE3	ENST00000517490.6	c.732+87C>T		intron_variant		1	NM_003909.5	ENSP00000477590	P1
CPNE3	ENST00000517391.5	c.398+87C>T		intron_variant		3		ENSP00000428561
CPNE3	ENST00000517862.1	n.246C>T		non_coding_transcript_exon_variant	2/2	3

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

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0354

Gnomad4 ASJ exome AF: 0.0991

Gnomad4 EAS exome AF: 0.0000362

Gnomad4 SAS exome AF: 0.0140

Gnomad4 FIN exome AF: 0.0583

Gnomad4 NFE exome AF: 0.0890

Gnomad4 OTH exome AF: 0.0674

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

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0444

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0570

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0454 Hom.: 32

Bravo AF: 0.0529

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs17609515; hg19: chr8-87557153;