rs10456444

Variant names:

• chr6-36755065-T-C
• rs10456444
• NM_020939.2:c.909+1180A>G

Variant summary

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

The NM_020939.2(CPNE5):​c.909+1180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,132 control chromosomes in the GnomAD database, including 14,960 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 0.44 (14958 hom., cov: 33)
  • Exomes 𝑓: 0.58 (2 hom.)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020939.2. 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
	CPNE5	NM_020939.2	MANE Select	c.909+1180A>G		intron	N/A	NP_065990.1
	CPNE5	NM_001410887.1		c.960+1180A>G		intron	N/A	NP_001397816.1
	CPNE5	NM_001376889.1		c.960+1180A>G		intron	N/A	NP_001363818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE5	ENST00000244751.7	TSL:1 MANE Select	c.909+1180A>G		intron	N/A	ENSP00000244751.2
	CPNE5	ENST00000393189.2	TSL:1	c.33+1180A>G		intron	N/A	ENSP00000376885.2
	CPNE5	ENST00000493411.2	TSL:1	n.151+1180A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66980 AN: 152004 Hom.: 14955 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.583 AC: 7 AN: 12 Hom.: 2 Cov.: 0 AF XY: 0.625 AC XY: 5 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.583 AC: 7 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.440 AC: 67001 AN: 152120 Hom.: 14958 Cov.: 33 AF XY: 0.433 AC XY: 32215 AN XY: 74374

African (AFR) AF: 0.433 AC: 17957 AN: 41472

American (AMR) AF: 0.382 AC: 5848 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2053 AN: 5166

South Asian (SAS) AF: 0.389 AC: 1878 AN: 4824

European-Finnish (FIN) AF: 0.383 AC: 4059 AN: 10594

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32238 AN: 67986

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.464 Hom.: 33569

Bravo AF: 0.441

Asia WGS AF: 0.347 AC: 1205 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		-0.28
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: rs10456444; hg19: chr6-36722842;