16-89589843-T-C

Variant summary

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

The NM_153636.3(CPNE7):c.1062-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,598,050 control chromosomes in the GnomAD database, including 237,167 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 0.52 (21134 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216033 hom.)
• Consequence: CPNE7 NM_153636.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

CPNE7 (HGNC:2320): (copine 7) This gene encodes a member of the copine family, which is composed of calcium-dependent membrane-binding proteins. The gene product contains two N-terminal C2 domains and one von Willebrand factor A domain. The encoded protein may be involved in membrane trafficking. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE7	NM_153636.3	c.1062-54T>C		intron_variant		ENST00000319518.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE7	ENST00000319518.13	c.1062-54T>C		intron_variant		1	NM_153636.3	P1
CPNE7	ENST00000268720.9	c.1287-54T>C		intron_variant		1
CPNE7	ENST00000529800.5	c.222-54T>C		intron_variant		5
CPNE7	ENST00000568977.1	c.6-54T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79656 AN: 151960 Hom.: 21102 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.544 AC: 787311 AN: 1445972 Hom.: 216033 AF XY: 0.547 AC XY: 393395 AN XY: 719774

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome AF: 0.524 AC: 79741 AN: 152078 Hom.: 21134 Cov.: 32 AF XY: 0.528 AC XY: 39278 AN XY: 74334

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.479

Alfa AF: 0.513 Hom.: 25850

Bravo AF: 0.518

Asia WGS AF: 0.687 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.029
Dann	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs464349; hg19: chr16-89656251; COSMIC: COSV52015701; COSMIC: COSV52015701;