3-132032208-T-C

Variant names:

• chr3-132032208-T-C
• rs9289410
• NM_130808.3:c.-2+2359A>G

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+2359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,348 control chromosomes in the GnomAD database, including 71,213 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 0.97 (71213 hom., cov: 32)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.984 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+2359A>G		intron	N/A	NP_570720.1
	CPNE4	NM_001289112.2		c.53+5349A>G		intron	N/A	NP_001276041.1
	CPNE4	NM_153429.2		c.53+5349A>G		intron	N/A	NP_702907.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE4	ENST00000429747.6	TSL:1 MANE Select	c.-2+2359A>G		intron	N/A	ENSP00000411904.1
	CPNE4	ENST00000512332.5	TSL:1	c.53+5349A>G		intron	N/A	ENSP00000424853.1
	CPNE4	ENST00000511604.5	TSL:1	c.-2+2359A>G		intron	N/A	ENSP00000423811.1

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146978 AN: 152230 Hom.: 71155 Cov.: 32

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.960

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.965 AC: 147091 AN: 152348 Hom.: 71213 Cov.: 32 AF XY: 0.963 AC XY: 71723 AN XY: 74488

African (AFR) AF: 0.992 AC: 41241 AN: 41582

American (AMR) AF: 0.882 AC: 13496 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3393 AN: 3472

East Asian (EAS) AF: 0.783 AC: 4047 AN: 5170

South Asian (SAS) AF: 0.944 AC: 4559 AN: 4828

European-Finnish (FIN) AF: 0.960 AC: 10196 AN: 10618

Middle Eastern (MID) AF: 0.983 AC: 287 AN: 292

European-Non Finnish (NFE) AF: 0.984 AC: 66943 AN: 68048

Other (OTH) AF: 0.961 AC: 2033 AN: 2116

Alfa AF: 0.976 Hom.: 19118

Bravo AF: 0.956

Asia WGS AF: 0.883 AC: 3071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.33
PhyloP100		0.18
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: rs9289410; hg19: chr3-131751052;