6-36751302-C-T

Position:

• chr6-36751302-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
CPNE5	NM_020939.2	c.971+1732G>A		intron_variant		ENST00000244751.7	NP_065990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7	c.971+1732G>A		intron_variant		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

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.266

Alfa AF: 0.282 Hom.: 2738

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

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: rs9986517; hg19: chr6-36719079;