Genetic Variant CPED1:c.750-3dupT (chr7-121099908-G-GT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_024913.5(CPED1):c.750-3dupT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. 1/1 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 0.00061 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0050 ( 0 hom. )

Consequence

CPED1
NM_024913.5 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

Publications

3 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: Uncertain_significance. The variant received 2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.05485232 fraction of the gene. Cryptic splice site detected, with MaxEntScore 13, offset of 0 (no position change), new splice context is: tgttttttttttttttttAGgaa. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	NM_024913.5	MANE Select	c.750-3dupT		splice_acceptor intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.750-3dupT		splice_acceptor intron	N/A	NP_001099003.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPED1	ENST00000310396.10	TSL:1 MANE Select	c.750-18_750-17insT	intron	N/A	ENSP00000309772.5
CPED1	ENST00000450913.6	TSL:1	c.750-18_750-17insT	intron	N/A	ENSP00000406122.2
CPED1	ENST00000423795.5	TSL:1	c.90-18_90-17insT	intron	N/A	ENSP00000415573.1

Frequencies

GnomAD3 genomes

AF:

0.000612

AC:

AN:

148730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

Gnomad ASJ

AF:

0.00320

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00213

Gnomad FIN

AF:

0.000928

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000179

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00692

AC:

1154

AN:

166798

AF XY:

0.00709

show subpopulations

Gnomad AFR exome

AF:

0.00851

Gnomad AMR exome

AF:

0.00572

Gnomad ASJ exome

AF:

0.00529

Gnomad EAS exome

AF:

0.00159

Gnomad FIN exome

AF:

0.00821

Gnomad NFE exome

AF:

0.00533

Gnomad OTH exome

AF:

0.00782

GnomAD4 exome

AF:

0.00502

AC:

6735

AN:

1340980

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

3458

AN XY:

668564

show subpopulations

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

African (AFR)

AF:

0.00748

AC:

222

AN:

29668

American (AMR)

AF:

0.00378

AC:

142

AN:

37562

Ashkenazi Jewish (ASJ)

AF:

0.00459

AC:

110

AN:

23948

East Asian (EAS)

AF:

0.000945

AC:

AN:

37048

South Asian (SAS)

AF:

0.0122

AC:

963

AN:

78820

European-Finnish (FIN)

AF:

0.00767

AC:

358

AN:

46650

Middle Eastern (MID)

AF:

0.000742

AC:

AN:

5388

European-Non Finnish (NFE)

AF:

0.00452

AC:

4638

AN:

1026430

Other (OTH)

AF:

0.00474

AC:

263

AN:

55466

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.284

Heterozygous variant carriers

532

1064

1595

2127

2659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

180

360

540

720

900

<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:

0.000612

AC:

AN:

148814

Hom.:

Cov.:

AF XY:

0.000594

AC XY:

AN XY:

72386

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

40604

American (AMR)

AF:

0.000133

AC:

AN:

15000

Ashkenazi Jewish (ASJ)

AF:

0.00320

AC:

AN:

3440

East Asian (EAS)

AF:

0.000197

AC:

AN:

5074

South Asian (SAS)

AF:

0.00213

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.000928

AC:

AN:

9698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000179

AC:

AN:

67064

Other (OTH)

AF:

0.00

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

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:

0.00528

Hom.:

136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

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

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7-121099908-GTTTTTTT-GTTTTTTTT

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