7-121099908-GTTTT-GTTTTT

Position:

• chr7-121099908-GTTTT-GTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.054527752 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPED1	NM_024913.5	c.750-3dupT		splice_acceptor_variant, intron_variant		ENST00000310396.10	NP_079189.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPED1	ENST00000310396.10	c.750-3dupT		splice_acceptor_variant, intron_variant		1	NM_024913.5	ENSP00000309772.5

Frequencies

GnomAD3 genomes AF: 0.000612 AC: 91 AN: 148730 Hom.: 0 Cov.: 0

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

GnomAD3 exomes AF: 0.00692 AC: 1154 AN: 166798 Hom.: 0 AF XY: 0.00709 AC XY: 644 AN XY: 90770

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 SAS exome AF: 0.0151

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.: 0 Cov.: 0 AF XY: 0.00517 AC XY: 3458 AN XY: 668564

Gnomad4 AFR exome AF: 0.00748

Gnomad4 AMR exome AF: 0.00378

Gnomad4 ASJ exome AF: 0.00459

Gnomad4 EAS exome AF: 0.000945

Gnomad4 SAS exome AF: 0.0122

Gnomad4 FIN exome AF: 0.00767

Gnomad4 NFE exome AF: 0.00452

Gnomad4 OTH exome AF: 0.00474

GnomAD4 genome AF: 0.000612 AC: 91 AN: 148814 Hom.: 0 Cov.: 0 AF XY: 0.000594 AC XY: 43 AN XY: 72386

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.000133

Gnomad4 ASJ AF: 0.00320

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00213

Gnomad4 FIN AF: 0.000928

Gnomad4 NFE AF: 0.000179

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs33990520; hg19: chr7-120739962;