6-36742292-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_020939.2(CPNE5):c.1758G>T(p.Ala586=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,598,008 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (29 hom.)
• Consequence: CPNE5 NM_020939.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.12

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-36742292-C-A is Benign according to our data. Variant chr6-36742292-C-A is described in ClinVar as [Benign]. Clinvar id is 786086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1732/152232) while in subpopulation AFR AF= 0.0392 (1627/41516). AF 95% confidence interval is 0.0376. There are 22 homozygotes in gnomad4. There are 801 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2	c.1758G>T	p.Ala586=	synonymous_variant	21/21	ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7	c.1758G>T	p.Ala586=	synonymous_variant	21/21	1	NM_020939.2	A1
CPNE5	ENST00000393189.2	c.882G>T	p.Ala294=	synonymous_variant	10/10	1
CPNE5	ENST00000633136.2	c.1809G>T	p.Ala603=	synonymous_variant	22/22	5		P3
CPNE5	ENST00000459703.5	n.1041G>T		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1728 AN: 152114 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00298 AC: 702 AN: 235596 Hom.: 19 AF XY: 0.00219 AC XY: 281 AN XY: 128048

Gnomad AFR exome AF: 0.0390

Gnomad AMR exome AF: 0.00228

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000681

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000930

Gnomad OTH exome AF: 0.000852

GnomAD4 exome AF: 0.00109 AC: 1582 AN: 1445776 Hom.: 29 Cov.: 31 AF XY: 0.000925 AC XY: 665 AN XY: 718694

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.00241

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000939

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000461

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.0114 AC: 1732 AN: 152232 Hom.: 22 Cov.: 32 AF XY: 0.0108 AC XY: 801 AN XY: 74426

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.0133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.32
Dann	Benign	0.57

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: rs150763631; hg19: chr6-36710069;