7-121099908-GTTTTTTT-GTTTTTT

Variant names:

• chr7-121099908-GT-G
• rs33990520
• NM_024913.5:c.750-3delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_024913.5(CPED1):​c.750-3delT variant causes a splice region, 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 0.19 (2969 hom., cov: 0)
  • Exomes 𝑓: 0.35 (1515 hom.)
  • Failed GnomAD Quality Control
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28104 AN: 148288 Hom.: 2971 Cov.: 0

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.318 AC: 52970 AN: 166798 AF XY: 0.325

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.424

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.339

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.347 AC: 387034 AN: 1114450 Hom.: 1515 Cov.: 0 AF XY: 0.349 AC XY: 193737 AN XY: 555802

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

African (AFR) AF: 0.247 AC: 5613 AN: 22742

American (AMR) AF: 0.291 AC: 8202 AN: 28218

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 8276 AN: 20034

East Asian (EAS) AF: 0.325 AC: 8239 AN: 25366

South Asian (SAS) AF: 0.351 AC: 24547 AN: 69998

European-Finnish (FIN) AF: 0.279 AC: 10895 AN: 39028

Middle Eastern (MID) AF: 0.351 AC: 1663 AN: 4734

European-Non Finnish (NFE) AF: 0.353 AC: 303516 AN: 858768

Other (OTH) AF: 0.353 AC: 16083 AN: 45562

⚠️ 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: 0.189 AC: 28109 AN: 148368 Hom.: 2969 Cov.: 0 AF XY: 0.187 AC XY: 13521 AN XY: 72122

African (AFR) AF: 0.0927 AC: 3760 AN: 40550

American (AMR) AF: 0.156 AC: 2324 AN: 14938

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1147 AN: 3432

East Asian (EAS) AF: 0.109 AC: 551 AN: 5066

South Asian (SAS) AF: 0.279 AC: 1305 AN: 4684

European-Finnish (FIN) AF: 0.173 AC: 1655 AN: 9558

Middle Eastern (MID) AF: 0.266 AC: 75 AN: 282

European-Non Finnish (NFE) AF: 0.250 AC: 16696 AN: 66904

Other (OTH) AF: 0.207 AC: 423 AN: 2044

Alfa AF: 0.295 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 (auto)

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;