rs7622210

Positions:

• chr3-132243465-A-G

Variant summary

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

The ENST00000512055.5(CPNE4):​c.-1829+40578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 270,668 control chromosomes in the GnomAD database, including 3,904 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 0.17 (2813 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1091 hom.)
• Consequence: CPNE4 ENST00000512055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

CPNE4 (HGNC:2317): (copine 4) This gene belongs to the highly conserved copine family. It encodes a calcium-dependent, phospholipid-binding protein, which may be involved in membrane trafficking, mitogenesis and development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE4	ENST00000512055.5	c.-1829+40578T>C		intron_variant		2		ENSP00000421705	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26404 AN: 152034 Hom.: 2800 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0880

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.130 AC: 15353 AN: 118516 Hom.: 1091 AF XY: 0.129 AC XY: 8487 AN XY: 66014

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.0858

Gnomad4 ASJ exome AF: 0.0952

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.174 AC: 26447 AN: 152152 Hom.: 2813 Cov.: 33 AF XY: 0.173 AC XY: 12843 AN XY: 74382

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0880

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.162

Alfa AF: 0.136 Hom.: 714

Bravo AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7622210; hg19: chr3-131962309;