7-121133900-A-G

Position:

• chr7-121133900-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000310396.10(CPED1):​c.1648+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,495,960 control chromosomes in the GnomAD database, including 127,620 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 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 0.34 (11004 hom., cov: 32)
  • Exomes 𝑓: 0.41 (116616 hom.)
• Consequence: CPED1 ENST00000310396.10 splice_region, intron
• Scores: Splicing: ADA: 0.0001293
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPED1	NM_024913.5	c.1648+7A>G		splice_region_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.1648+7A>G		splice_region_variant, intron_variant		1	NM_024913.5	ENSP00000309772	P1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51496 AN: 151858 Hom.: 11001 Cov.: 32

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.436 AC: 100947 AN: 231516 Hom.: 24132 AF XY: 0.434 AC XY: 54525 AN XY: 125546

Gnomad AFR exome AF: 0.0757

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.632

Gnomad SAS exome AF: 0.410

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.438

GnomAD4 exome AF: 0.408 AC: 548735 AN: 1343984 Hom.: 116616 Cov.: 20 AF XY: 0.409 AC XY: 275469 AN XY: 673508

Gnomad4 AFR exome AF: 0.0706

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.339 AC: 51498 AN: 151976 Hom.: 11004 Cov.: 32 AF XY: 0.345 AC XY: 25657 AN XY: 74278

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.375

Alfa AF: 0.378 Hom.: 3785

Bravo AF: 0.341

Asia WGS AF: 0.439 AC: 1522 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		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: rs61128227; hg19: chr7-120773954; COSMIC: COSV59998976; COSMIC: COSV59998976;