7-121125900-T-C

Position:

• chr7-121125900-T-C

Variant summary

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

The NM_024913.5(CPED1):​c.1134+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,589,932 control chromosomes in the GnomAD database, including 177,706 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 0.44 (16147 hom., cov: 32)
  • Exomes 𝑓: 0.47 (161559 hom.)
• Consequence: CPED1 NM_024913.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004039
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPED1	NM_024913.5	c.1134+8T>C		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.1134+8T>C		splice_region_variant, intron_variant		1	NM_024913.5	ENSP00000309772.5

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67303 AN: 151950 Hom.: 16142 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.460

GnomAD3 exomes AF: 0.503 AC: 125924 AN: 250366 Hom.: 33986 AF XY: 0.497 AC XY: 67205 AN XY: 135300

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.660

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.841

Gnomad SAS exome AF: 0.435

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.465 AC: 669013 AN: 1437866 Hom.: 161559 Cov.: 27 AF XY: 0.465 AC XY: 333180 AN XY: 716826

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.657

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.848

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.443 AC: 67325 AN: 152066 Hom.: 16147 Cov.: 32 AF XY: 0.451 AC XY: 33526 AN XY: 74316

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.455

Alfa AF: 0.448 Hom.: 26193

Bravo AF: 0.445

Asia WGS AF: 0.583 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.4
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.16		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: rs798949; hg19: chr7-120765954;