7-121099908-GTTTTTTT-GTTTT

Variant names:

• chr7-121099908-GTTT-G
• rs33990520
• NM_024913.5:c.750-5_750-3delTTT

Variant summary

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

The NM_024913.5(CPED1):​c.750-5_750-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00767 in 1,464,776 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 0.00046 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0085 (0 hom.)
• Consequence: CPED1 NM_024913.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 3 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: Variant has high frequency in the AMR (0.0173) population. However there is too low homozygotes in high coverage region: (expected more than 21, got 0).

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.750-5_750-3delTTT		splice_region intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.750-5_750-3delTTT		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_750-15delTTT		intron	N/A	ENSP00000309772.5
	CPED1	ENST00000450913.6	TSL:1	c.750-17_750-15delTTT		intron	N/A	ENSP00000406122.2
	CPED1	ENST00000423795.5	TSL:1	c.90-17_90-15delTTT		intron	N/A	ENSP00000415573.1

Frequencies

GnomAD3 genomes AF: 0.000457 AC: 68 AN: 148686 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000786

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000516

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000686

Gnomad OTH AF: 0.000985

GnomAD2 exomes AF: 0.0162 AC: 2704 AN: 166798 AF XY: 0.0162

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.0160

Gnomad EAS exome AF: 0.0185

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.00849 AC: 11168 AN: 1316006 Hom.: 0 AF XY: 0.00826 AC XY: 5424 AN XY: 656298

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

African (AFR) AF: 0.0121 AC: 352 AN: 29000

American (AMR) AF: 0.0185 AC: 672 AN: 36306

Ashkenazi Jewish (ASJ) AF: 0.00984 AC: 231 AN: 23484

East Asian (EAS) AF: 0.0104 AC: 369 AN: 35380

South Asian (SAS) AF: 0.00720 AC: 563 AN: 78238

European-Finnish (FIN) AF: 0.0128 AC: 584 AN: 45716

Middle Eastern (MID) AF: 0.00564 AC: 30 AN: 5316

European-Non Finnish (NFE) AF: 0.00780 AC: 7865 AN: 1008140

Other (OTH) AF: 0.00922 AC: 502 AN: 54426

⚠️ 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 AF: 0.000464 AC: 69 AN: 148770 Hom.: 0 Cov.: 0 AF XY: 0.000442 AC XY: 32 AN XY: 72360

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

African (AFR) AF: 0.000246 AC: 10 AN: 40598

American (AMR) AF: 0.000133 AC: 2 AN: 14990

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

East Asian (EAS) AF: 0.000788 AC: 4 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4692

European-Finnish (FIN) AF: 0.000516 AC: 5 AN: 9682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000686 AC: 46 AN: 67052

Other (OTH) AF: 0.000976 AC: 2 AN: 2050

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000126138), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0161 Hom.: 136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs33990520; hg19: chr7-120739962;