7-121099908-GTTTTTTT-GTT

Variant names:

• chr7-121099908-GTTTTT-G
• rs33990520
• NM_024913.5:c.750-7_750-3delTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024913.5(CPED1):​c.750-7_750-3delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,346,802 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPED1 NM_024913.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 publications found

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]

ACMG classification

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.750-7_750-3delTTTTT		splice_region intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.750-7_750-3delTTTTT		splice_region intron	N/A	NP_001099003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	ENST00000310396.10	TSL:1 MANE Select	c.750-17_750-13delTTTTT		intron	N/A	ENSP00000309772.5
	CPED1	ENST00000450913.6	TSL:1	c.750-17_750-13delTTTTT		intron	N/A	ENSP00000406122.2
	CPED1	ENST00000423795.5	TSL:1	c.90-17_90-13delTTTTT		intron	N/A	ENSP00000415573.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 148736 Hom.: 0 Cov.: 0

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1346802 Hom.: 0 AF XY: 0.00000149 AC XY: 1 AN XY: 671616

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

African (AFR) AF: 0.00 AC: 0 AN: 29856

American (AMR) AF: 0.00 AC: 0 AN: 37656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24014

East Asian (EAS) AF: 0.00 AC: 0 AN: 37084

South Asian (SAS) AF: 0.00 AC: 0 AN: 79550

European-Finnish (FIN) AF: 0.0000426 AC: 2 AN: 46906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5398

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1030642

Other (OTH) AF: 0.00 AC: 0 AN: 55696

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 148736 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72288

African (AFR) AF: 0.00 AC: 0 AN: 40502

American (AMR) AF: 0.00 AC: 0 AN: 14978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67078

Other (OTH) AF: 0.00 AC: 0 AN: 2030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs33990520; hg19: chr7-120739962;