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. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376895.1. 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
	CPNE5	NM_020939.2	MANE Select	c.1563+60C>T		intron	N/A	NP_065990.1	Q9HCH3-1
	CPNE5	NM_001376895.1		c.747C>T	p.Asp249Asp	synonymous	Exon 9 of 9	NP_001363824.1
	CPNE5	NM_001376892.1		c.573C>T	p.Asp191Asp	synonymous	Exon 8 of 8	NP_001363821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE5	ENST00000244751.7	TSL:1 MANE Select	c.1563+60C>T		intron	N/A	ENSP00000244751.2	Q9HCH3-1
	CPNE5	ENST00000393189.2	TSL:1	c.687+60C>T		intron	N/A	ENSP00000376885.2	Q9HCH3-2
	CPNE5	ENST00000493411.2	TSL:1	n.743+60C>T		intron	N/A

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

African (AFR) AF: 0.244 AC: 7758 AN: 31768

American (AMR) AF: 0.161 AC: 7125 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 9066 AN: 25332

East Asian (EAS) AF: 0.194 AC: 7591 AN: 39138

South Asian (SAS) AF: 0.237 AC: 19909 AN: 84166

European-Finnish (FIN) AF: 0.282 AC: 14321 AN: 50762

Middle Eastern (MID) AF: 0.299 AC: 1629 AN: 5440

European-Non Finnish (NFE) AF: 0.365 AC: 376991 AN: 1032674

Other (OTH) AF: 0.319 AC: 18281 AN: 57230

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

African (AFR) AF: 0.252 AC: 10476 AN: 41542

American (AMR) AF: 0.223 AC: 3419 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1065 AN: 5172

South Asian (SAS) AF: 0.217 AC: 1049 AN: 4830

European-Finnish (FIN) AF: 0.269 AC: 2849 AN: 10600

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24526 AN: 68006

Other (OTH) AF: 0.273 AC: 578 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.077
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: rs3213534; hg19: chr6-36711406; COSMIC: COSV55200899; COSMIC: COSV55200899;