6-36743273-A-G

Position:

• chr6-36743273-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376895.1(CPNE5):​c.*17T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 979,348 control chromosomes in the GnomAD database, including 134,807 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 0.51 (20489 hom., cov: 32)
  • Exomes 𝑓: 0.52 (114318 hom.)
• Consequence: CPNE5 NM_001376895.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE5	NM_020939.2	c.1563+416T>C		intron_variant		ENST00000244751.7	NP_065990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7	c.1563+416T>C		intron_variant		1	NM_020939.2	ENSP00000244751.2

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77841 AN: 151934 Hom.: 20442 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.482

GnomAD4 exome AF: 0.524 AC: 433598 AN: 827294 Hom.: 114318 Cov.: 18 AF XY: 0.523 AC XY: 199871 AN XY: 382288

Gnomad4 AFR exome AF: 0.617

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.513 AC: 77939 AN: 152054 Hom.: 20489 Cov.: 32 AF XY: 0.504 AC XY: 37493 AN XY: 74318

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.488

Alfa AF: 0.501 Hom.: 31536

Bravo AF: 0.508

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.36
DANN	Benign	0.65

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: rs7763347; hg19: chr6-36711050;