Genetic Variant NM_024913.5:c.416C>T (chr7-121015831-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024913.5(CPED1):c.416C>T(p.Pro139Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,557,954 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

CPED1
NM_024913.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.349

Publications

4 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032708943).

BP6

Variant 7-121015831-C-T is Benign according to our data. Variant chr7-121015831-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 736845.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024913.5. 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
	CPED1	NM_024913.5	MANE Select	c.416C>T	p.Pro139Leu	missense	Exon 3 of 23	NP_079189.4
	CPED1	NM_001105533.1		c.416C>T	p.Pro139Leu	missense	Exon 2 of 18	NP_001099003.1	Q9H6Q5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPED1	ENST00000310396.10	TSL:1 MANE Select	c.416C>T	p.Pro139Leu	missense	Exon 3 of 23	ENSP00000309772.5	A4D0V7-1
CPED1	ENST00000450913.6	TSL:1	c.416C>T	p.Pro139Leu	missense	Exon 2 of 18	ENSP00000406122.2	A4D0V7-2
CPED1	ENST00000495036.5	TSL:1	n.863C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000420

AC:

AN:

202310

AF XY:

0.000271

show subpopulations

Gnomad AFR exome

AF:

0.00313

Gnomad AMR exome

AF:

0.000537

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.000885

GnomAD4 exome

AF:

0.000299

AC:

420

AN:

1405686

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

220

AN XY:

696962

show subpopulations

African (AFR)

AF:

0.00261

AC:

AN:

30272

American (AMR)

AF:

0.000849

AC:

AN:

31800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23962

East Asian (EAS)

AF:

0.0000268

AC:

AN:

37284

South Asian (SAS)

AF:

0.00

AC:

AN:

75546

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52494

Middle Eastern (MID)

AF:

0.000718

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.000259

AC:

283

AN:

1090742

Other (OTH)

AF:

0.000431

AC:

AN:

58012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000939

AC:

143

AN:

152268

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00274

AC:

114

AN:

41538

American (AMR)

AF:

0.000981

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68032

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000561

Hom.:

Bravo

AF:

0.00130

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.1

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.00055

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00085

LIST_S2

Benign

0.41

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PhyloP100

-0.35

PrimateAI

Benign

0.27

PROVEAN

Benign

0.36

REVEL

Benign

0.026

Sift

Benign

0.36

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.13

MVP

0.030

MPC

0.055

ClinPred

0.0055

GERP RS

0.42

Varity_R

0.022

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over