rs6775745

Positions:

• chr3-132095056-G-A
• chr3-132095056-G-T

Variant summary

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

The ENST00000512055.5(CPNE4):​c.-1828-54735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 151,490 control chromosomes in the GnomAD database, including 2,423 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 (2423 hom., cov: 32)
• Consequence: CPNE4 ENST00000512055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE4	ENST00000512055.5	c.-1828-54735C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26449 AN: 151390 Hom.: 2420 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26464 AN: 151490 Hom.: 2423 Cov.: 32 AF XY: 0.174 AC XY: 12873 AN XY: 73958

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.194

Alfa AF: 0.182 Hom.: 3411

Bravo AF: 0.170

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6775745; hg19: chr3-131813900;