7-121099908-GTTTTTTT-GTTTTTTTTTTTT

Variant names:

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

Variant summary

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

The NM_024913.5(CPED1):​c.750-7_750-3dupTTTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: CPED1 NM_024913.5 splice_acceptor, 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.

• 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: ttttttttttttttttttAGgaa. 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.750-7_750-3dupTTTTT		splice_acceptor intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.750-7_750-3dupTTTTT		splice_acceptor 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.750-18_750-17insTTTTT		intron	N/A	ENSP00000309772.5
	CPED1	ENST00000450913.6	TSL:1	c.750-18_750-17insTTTTT		intron	N/A	ENSP00000406122.2
	CPED1	ENST00000423795.5	TSL:1	c.90-18_90-17insTTTTT		intron	N/A	ENSP00000415573.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 7.42e-7 AC: 1 AN: 1346860 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 671646

⚠️ 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: 0.00 AC: 0 AN: 46908

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

European-Non Finnish (NFE) AF: 9.70e-7 AC: 1 AN: 1030694

Other (OTH) AF: 0.00 AC: 0 AN: 55700

⚠️ 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 Cov.: 0

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;