Variant 7-120989625-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024913.5(CPED1):c.4G>A(p.Val2Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,613,818 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000085 ( 1 hom. )

Consequence

CPED1
NM_024913.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

CPED1 (HGNC:26159): (cadherin like and PC-esterase domain containing 1) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

CPED1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12842971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPED1	NM_024913.5 link	c.4G>A	p.Val2Ile	missense_variant	2/23	ENST00000310396.10	NP_079189.4	A4D0V7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPED1	ENST00000310396.10 link	c.4G>A	p.Val2Ile	missense_variant	2/23	1	NM_024913.5	ENSP00000309772.5		A4D0V7-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251214

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.0000848

AC:

124

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000921

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000621

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000137

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.4G>A (p.V2I) alteration is located in exon 2 (coding exon 1) of the CPED1 gene. This alteration results from a G to A substitution at nucleotide position 4, causing the valine (V) at amino acid position 2 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0043

T;T;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;.;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.23

N;N;N;N

REVEL

Benign

0.027

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.20

T;D;T;T

Polyphen

0.022

B;.;.;B

Vest4

0.076

MVP

0.27

MPC

0.047

ClinPred

0.022

GERP RS

1.7

Varity_R

0.038

gMVP

0.086

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over