rs452176

Variant names:

• chr16-89586624-G-A
• rs452176
• NM_153636.3:c.781-46G>A

Variant summary

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

The NM_153636.3(CPNE7):​c.781-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,512,934 control chromosomes in the GnomAD database, including 221,409 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 0.48 (18696 hom., cov: 27)
  • Exomes 𝑓: 0.54 (202713 hom.)
• Consequence: CPNE7 NM_153636.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE7	NM_153636.3	c.781-46G>A		intron_variant	Intron 7 of 14	ENST00000319518.13	NP_705900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE7	ENST00000319518.13	c.781-46G>A		intron_variant	Intron 7 of 14	1	NM_153636.3	ENSP00000317374.8
CPNE7	ENST00000268720.9	c.1006-46G>A		intron_variant	Intron 9 of 16	1		ENSP00000268720.5
CPNE7	ENST00000532500.1	n.227-46G>A		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.477 AC: 71993 AN: 150780 Hom.: 18687 Cov.: 27

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.524 AC: 130107 AN: 248496 AF XY: 0.524

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.286

Gnomad FIN exome AF: 0.619

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.540 AC: 735574 AN: 1362036 Hom.: 202713 Cov.: 20 AF XY: 0.539 AC XY: 368007 AN XY: 683288

African (AFR) AF: 0.255 AC: 8001 AN: 31400

American (AMR) AF: 0.625 AC: 27727 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 14140 AN: 25442

East Asian (EAS) AF: 0.347 AC: 13558 AN: 39100

South Asian (SAS) AF: 0.439 AC: 36914 AN: 84040

European-Finnish (FIN) AF: 0.624 AC: 32789 AN: 52542

Middle Eastern (MID) AF: 0.565 AC: 3135 AN: 5548

European-Non Finnish (NFE) AF: 0.556 AC: 569025 AN: 1022566

Other (OTH) AF: 0.531 AC: 30285 AN: 57002

GnomAD4 genome AF: 0.477 AC: 72016 AN: 150898 Hom.: 18696 Cov.: 27 AF XY: 0.480 AC XY: 35332 AN XY: 73660

African (AFR) AF: 0.267 AC: 10952 AN: 41038

American (AMR) AF: 0.584 AC: 8877 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1893 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1533 AN: 5012

South Asian (SAS) AF: 0.403 AC: 1916 AN: 4760

European-Finnish (FIN) AF: 0.622 AC: 6495 AN: 10436

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38525 AN: 67680

Other (OTH) AF: 0.536 AC: 1125 AN: 2098

Alfa AF: 0.551 Hom.: 31206

Bravo AF: 0.470

Asia WGS AF: 0.374 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.35
PhyloP100		0.17
PromoterAI		-0.0042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs452176; hg19: chr16-89653032; COSMIC: COSV52012448; COSMIC: COSV52012448;