6-36751302-C-T

Variant names:

• chr6-36751302-C-T
• rs9986517
• NM_020939.2:c.971+1732G>A

Variant summary

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

The NM_020939.2(CPNE5):​c.971+1732G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,054 control chromosomes in the GnomAD database, including 6,663 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 0.29 (6663 hom., cov: 32)
• Consequence: CPNE5 NM_020939.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE5	NM_020939.2	c.971+1732G>A		intron_variant	Intron 14 of 20	ENST00000244751.7	NP_065990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7	c.971+1732G>A		intron_variant	Intron 14 of 20	1	NM_020939.2	ENSP00000244751.2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44441 AN: 151936 Hom.: 6657 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44477 AN: 152054 Hom.: 6663 Cov.: 32 AF XY: 0.286 AC XY: 21259 AN XY: 74338

African (AFR) AF: 0.314 AC: 13033 AN: 41462

American (AMR) AF: 0.201 AC: 3069 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3464

East Asian (EAS) AF: 0.207 AC: 1074 AN: 5178

South Asian (SAS) AF: 0.199 AC: 959 AN: 4814

European-Finnish (FIN) AF: 0.254 AC: 2687 AN: 10562

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21746 AN: 67960

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.286 Hom.: 3158

Bravo AF: 0.288

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.97
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: rs9986517; hg19: chr6-36719079;