Genetic Variant CPED1:p.Ala551Val (chr7-121136043-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024913.5(CPED1):c.1652C>T(p.Ala551Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,343,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CPED1
NM_024913.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.579

Publications

30 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPED1	NM_024913.5 link	c.1652C>T	p.Ala551Val	missense_variant	Exon 14 of 23	ENST00000310396.10	NP_079189.4	A4D0V7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPED1	ENST00000310396.10 link	c.1652C>T	p.Ala551Val	missense_variant	Exon 14 of 23	1	NM_024913.5	ENSP00000309772.5	A4D0V7-1
CPED1	ENST00000450913.6 link	c.1652C>T	p.Ala551Val	missense_variant	Exon 13 of 18	1		ENSP00000406122.2	A4D0V7-2
CPED1	ENST00000423795.5 link	c.992C>T	p.Ala331Val	missense_variant	Exon 11 of 16	1		ENSP00000415573.1	G5E9U2
CPED1	ENST00000443817.1 link	c.992C>T	p.Ala331Val	missense_variant	Exon 10 of 10	1		ENSP00000391952.1	E9PCC8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149658

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1343724

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

667138

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28818

American (AMR)

AF:

0.00

AC:

AN:

26164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23204

East Asian (EAS)

AF:

0.00

AC:

AN:

33920

South Asian (SAS)

AF:

0.00

AC:

AN:

67608

European-Finnish (FIN)

AF:

0.0000198

AC:

AN:

50620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5282

European-Non Finnish (NFE)

AF:

9.50e-7

AC:

AN:

1053030

Other (OTH)

AF:

0.00

AC:

AN:

55078

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72902

African (AFR)

AF:

0.00

AC:

AN:

40566

American (AMR)

AF:

0.00

AC:

AN:

15058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67462

Other (OTH)

AF:

0.00

AC:

AN:

2056

Alfa

AF:

0.00

Hom.:

11784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.0020

T;.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.45

T;T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.047

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.85

L;L;.;.

PhyloP100

-0.58

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.13

N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.53

T;T;T;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.044

MutPred

0.43

Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);.;.;

MVP

0.040

MPC

0.054

ClinPred

0.036

GERP RS

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.33

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.33

Position offset: -3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over