Genetic Variant CPED1:c.750-6_750-3delTTTT (chr7-121099908-GTTTT-G) – 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.750-6_750-3delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000401 in 1,494,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

CPED1
NM_024913.5 splice_region, 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:

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;

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.750-6_750-3delTTTT		splice_region intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.750-6_750-3delTTTT		splice_region intron	N/A	NP_001099003.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPED1	ENST00000310396.10	TSL:1 MANE Select	c.750-17_750-14delTTTT	intron	N/A	ENSP00000309772.5
CPED1	ENST00000450913.6	TSL:1	c.750-17_750-14delTTTT	intron	N/A	ENSP00000406122.2
CPED1	ENST00000423795.5	TSL:1	c.90-17_90-14delTTTT	intron	N/A	ENSP00000415573.1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

148732

Hom.:

Cov.:

show subpopulations

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:

0.0000596

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000719

AC:

AN:

166798

AF XY:

0.0000771

show subpopulations

Gnomad AFR exome

AF:

0.0000925

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.0000760

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.0000416

AC:

AN:

1345842

Hom.:

AF XY:

0.0000492

AC XY:

AN XY:

671150

show subpopulations

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

African (AFR)

AF:

0.0000335

AC:

AN:

29832

American (AMR)

AF:

0.0000266

AC:

AN:

37606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24002

East Asian (EAS)

AF:

0.0000270

AC:

AN:

37066

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79522

European-Finnish (FIN)

AF:

0.000149

AC:

AN:

46868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5398

European-Non Finnish (NFE)

AF:

0.0000418

AC:

AN:

1029890

Other (OTH)

AF:

0.0000359

AC:

AN:

55658

⚠️ 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: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000269

AC:

AN:

148732

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

72286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40500

American (AMR)

AF:

0.00

AC:

AN:

14980

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000596

AC:

AN:

67078

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

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

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

7-121099908-GTTTTTTT-GTTT

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