Genetic Variant CPED1:c.1134+8T>C (chr7-121125900-T-C) – 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.1134+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,589,932 control chromosomes in the GnomAD database, including 177,706 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 16147 hom., cov: 32)

Exomes 𝑓: 0.47 ( 161559 hom. )

Consequence

CPED1
NM_024913.5 splice_region, intron

Scores

Splicing: ADA: 0.00004039

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.115

Publications

16 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.1134+8T>C		splice_region_variant, intron_variant	Intron 9 of 22	ENST00000310396.10	NP_079189.4	A4D0V7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPED1	ENST00000310396.10 link	c.1134+8T>C		splice_region_variant, intron_variant	Intron 9 of 22	1	NM_024913.5	ENSP00000309772.5		A4D0V7-1

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67303

AN:

151950

Hom.:

16142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.845

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.460

GnomAD2 exomes

AF:

0.503

AC:

125924

AN:

250366

AF XY:

0.497

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.660

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.841

Gnomad FIN exome

AF:

0.519

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.465

AC:

669013

AN:

1437866

Hom.:

161559

Cov.:

AF XY:

0.465

AC XY:

333180

AN XY:

716826

show subpopulations

African (AFR)

AF:

0.294

AC:

9710

AN:

33034

American (AMR)

AF:

0.657

AC:

29311

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

10214

AN:

25984

East Asian (EAS)

AF:

0.848

AC:

33517

AN:

39542

South Asian (SAS)

AF:

0.442

AC:

37881

AN:

85722

European-Finnish (FIN)

AF:

0.517

AC:

27511

AN:

53202

Middle Eastern (MID)

AF:

0.470

AC:

2680

AN:

5708

European-Non Finnish (NFE)

AF:

0.449

AC:

489932

AN:

1090454

Other (OTH)

AF:

0.474

AC:

28257

AN:

59586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

15186

30371

45557

60742

75928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14716

29432

44148

58864

73580

<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:

0.443

AC:

67325

AN:

152066

Hom.:

16147

Cov.:

AF XY:

0.451

AC XY:

33526

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.298

AC:

12364

AN:

41478

American (AMR)

AF:

0.602

AC:

9197

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1288

AN:

3472

East Asian (EAS)

AF:

0.845

AC:

4363

AN:

5166

South Asian (SAS)

AF:

0.448

AC:

2156

AN:

4812

European-Finnish (FIN)

AF:

0.521

AC:

5502

AN:

10566

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30797

AN:

67980

Other (OTH)

AF:

0.455

AC:

960

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1817

3633

5450

7266

9083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.450

Hom.:

34661

Bravo

AF:

0.445

Asia WGS

AF:

0.583

AC:

2024

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.4

(source)

DANN

Benign

0.51

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.16

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