3-131997261-C-A

Variant names:

• chr3-131997261-C-A
• rs9834560
• NM_130808.3:c.-2+37306G>T

Variant summary

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

The NM_130808.3(CPNE4):​c.-2+37306G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,852 control chromosomes in the GnomAD database, including 13,380 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 0.42 (13380 hom., cov: 31)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 11 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130808.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE4	NM_130808.3	MANE Select	c.-2+37306G>T		intron	N/A	NP_570720.1	Q96A23-1
	CPNE4	NM_001289112.2		c.53+40296G>T		intron	N/A	NP_001276041.1	Q96A23-2
	CPNE4	NM_153429.2		c.53+40296G>T		intron	N/A	NP_702907.1	Q96A23-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE4	ENST00000429747.6	TSL:1 MANE Select	c.-2+37306G>T		intron	N/A	ENSP00000411904.1	Q96A23-1
	CPNE4	ENST00000512332.5	TSL:1	c.53+40296G>T		intron	N/A	ENSP00000424853.1	Q96A23-2
	CPNE4	ENST00000511604.5	TSL:1	c.-2+37306G>T		intron	N/A	ENSP00000423811.1	Q96A23-1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63688 AN: 151734 Hom.: 13359 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.420 AC: 63750 AN: 151852 Hom.: 13380 Cov.: 31 AF XY: 0.421 AC XY: 31216 AN XY: 74212

African (AFR) AF: 0.446 AC: 18445 AN: 41392

American (AMR) AF: 0.494 AC: 7536 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3466

East Asian (EAS) AF: 0.515 AC: 2644 AN: 5138

South Asian (SAS) AF: 0.381 AC: 1831 AN: 4810

European-Finnish (FIN) AF: 0.370 AC: 3912 AN: 10562

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.393 AC: 26717 AN: 67924

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.405 Hom.: 37056

Bravo AF: 0.433

Asia WGS AF: 0.434 AC: 1510 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9834560; hg19: chr3-131716105;