rs3213534

Variant names:

• chr6-36743629-G-A
• rs3213534
• NM_020939.2:c.1563+60C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-36743629-G-A
• chr6-36743629-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001376895.1(CPNE5):​c.747C>T​(p.Asp249Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,523,048 control chromosomes in the GnomAD database, including 88,002 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 0.30 (7088 hom., cov: 33)
  • Exomes 𝑓: 0.34 (80914 hom.)
• Consequence: CPNE5 NM_001376895.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

Genes affected

CPNE5 (HGNC:2318): (copine 5) 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. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.077 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE5	NM_020939.2	c.1563+60C>T		intron_variant	Intron 20 of 20	ENST00000244751.7	NP_065990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7	c.1563+60C>T		intron_variant	Intron 20 of 20	1	NM_020939.2	ENSP00000244751.2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45579 AN: 152136 Hom.: 7088 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.338 AC: 462671 AN: 1370794 Hom.: 80914 AF XY: 0.335 AC XY: 229264 AN XY: 684796

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.358

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.365

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.299 AC: 45599 AN: 152254 Hom.: 7088 Cov.: 33 AF XY: 0.292 AC XY: 21710 AN XY: 74442

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.273

Alfa AF: 0.324 Hom.: 1282

Bravo AF: 0.292

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.55

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: rs3213534; hg19: chr6-36711406; COSMIC: COSV55200899; COSMIC: COSV55200899;