Genetic Variant CPED1:p.Ala551Gly (chr7-121136043-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024913.5(CPED1):c.1652C>G(p.Ala551Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,480,188 control chromosomes in the GnomAD database, including 156,829 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.43 ( 15347 hom., cov: 29)

Exomes 𝑓: 0.45 ( 141482 hom. )

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1098183E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPED1	NM_024913.5 link	c.1652C>G	p.Ala551Gly	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>G	p.Ala551Gly	missense_variant	Exon 14 of 23	1	NM_024913.5	ENSP00000309772.5	A4D0V7-1
CPED1	ENST00000450913.6 link	c.1652C>G	p.Ala551Gly	missense_variant	Exon 13 of 18	1		ENSP00000406122.2	A4D0V7-2
CPED1	ENST00000423795.5 link	c.992C>G	p.Ala331Gly	missense_variant	Exon 11 of 16	1		ENSP00000415573.1	G5E9U2
CPED1	ENST00000443817.1 link	c.992C>G	p.Ala331Gly	missense_variant	Exon 10 of 10	1		ENSP00000391952.1	E9PCC8

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

64556

AN:

149568

Hom.:

15343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.625

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.845

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.464

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.455

GnomAD2 exomes

AF:

0.460

AC:

82685

AN:

179686

AF XY:

0.459

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.364

Gnomad EAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.434

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.451

AC:

599981

AN:

1330512

Hom.:

141482

Cov.:

AF XY:

0.451

AC XY:

298003

AN XY:

660864

show subpopulations

African (AFR)

AF:

0.233

AC:

6658

AN:

28592

American (AMR)

AF:

0.610

AC:

15817

AN:

25940

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

8678

AN:

23036

East Asian (EAS)

AF:

0.842

AC:

28464

AN:

33800

South Asian (SAS)

AF:

0.421

AC:

28256

AN:

67042

European-Finnish (FIN)

AF:

0.512

AC:

25815

AN:

50446

Middle Eastern (MID)

AF:

0.455

AC:

2383

AN:

5240

European-Non Finnish (NFE)

AF:

0.440

AC:

458850

AN:

1041818

Other (OTH)

AF:

0.459

AC:

25060

AN:

54598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

13064

26128

39192

52256

65320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14112

28224

42336

56448

70560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.431

AC:

64568

AN:

149676

Hom.:

15347

Cov.:

AF XY:

0.441

AC XY:

32171

AN XY:

72982

show subpopulations

African (AFR)

AF:

0.255

AC:

10379

AN:

40658

American (AMR)

AF:

0.597

AC:

8990

AN:

15062

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1284

AN:

3460

East Asian (EAS)

AF:

0.845

AC:

4322

AN:

5114

South Asian (SAS)

AF:

0.453

AC:

2154

AN:

4756

European-Finnish (FIN)

AF:

0.531

AC:

5269

AN:

9926

Middle Eastern (MID)

AF:

0.437

AC:

125

AN:

286

European-Non Finnish (NFE)

AF:

0.453

AC:

30542

AN:

67430

Other (OTH)

AF:

0.450

AC:

934

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1723

3446

5169

6892

8615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.448

Hom.:

11784

Bravo

AF:

0.429

TwinsUK

AF:

0.447

AC:

1657

ALSPAC

AF:

0.450

AC:

1735

ESP6500AA

AF:

0.258

AC:

1135

ESP6500EA

AF:

0.441

AC:

3790

ExAC

AF:

0.478

AC:

57656

Asia WGS

AF:

0.573

AC:

1954

AN:

3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.88

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0021

T;.;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.30

T;T;T;T

MetaRNN

Benign

0.0000021

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;.;.

PhyloP100

-0.58

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Benign

0.0020

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.45

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.064

MPC

0.054

ClinPred

0.010

GERP RS

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over