3-131994722-G-T

Variant names:

• chr3-131994722-G-T
• rs1320900
• NM_130808.3:c.-2+39845C>A

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+39845C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,032 control chromosomes in the GnomAD database, including 6,718 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 0.28 (6718 hom., cov: 33)
• Consequence: CPNE4 NM_130808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE4	NM_130808.3	c.-2+39845C>A		intron_variant	Intron 1 of 15	ENST00000429747.6	NP_570720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE4	ENST00000429747.6	c.-2+39845C>A		intron_variant	Intron 1 of 15	1	NM_130808.3	ENSP00000411904.1
CPNE4	ENST00000511604.5	c.-2+39845C>A		intron_variant	Intron 4 of 18	1		ENSP00000423811.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43228 AN: 151914 Hom.: 6710 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.284 AC: 43239 AN: 152032 Hom.: 6718 Cov.: 33 AF XY: 0.287 AC XY: 21320 AN XY: 74294

African (AFR) AF: 0.154 AC: 6395 AN: 41492

American (AMR) AF: 0.405 AC: 6178 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3468

East Asian (EAS) AF: 0.375 AC: 1935 AN: 5160

South Asian (SAS) AF: 0.337 AC: 1619 AN: 4804

European-Finnish (FIN) AF: 0.298 AC: 3144 AN: 10566

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21967 AN: 67968

Other (OTH) AF: 0.311 AC: 659 AN: 2116

Alfa AF: 0.312 Hom.: 32362

Bravo AF: 0.289

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.42
PhyloP100		0.29
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: rs1320900; hg19: chr3-131713566;