rs41281692

Positions:

• chr7-121136043-C-A
• chr7-121136043-C-G
• chr7-121136043-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024913.5(CPED1):​c.1652C>A​(p.Ala551Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A551G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPED1 NM_024913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06931308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPED1	NM_024913.5	c.1652C>A	p.Ala551Glu	missense_variant	14/23	ENST00000310396.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPED1	ENST00000310396.10	c.1652C>A	p.Ala551Glu	missense_variant	14/23	1	NM_024913.5	P1
CPED1	ENST00000450913.6	c.1652C>A	p.Ala551Glu	missense_variant	13/18	1
CPED1	ENST00000423795.5	c.992C>A	p.Ala331Glu	missense_variant	11/16	1
CPED1	ENST00000443817.1	c.992C>A	p.Ala331Glu	missense_variant	10/10	1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1343736 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 667146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.099
DANN	Benign	0.58
DEOGEN2	Benign	0.0019	T;.;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.35	T;T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.75	N;N;N;N
REVEL	Benign	0.011
Sift	Benign	0.27	T;T;T;D
Sift4G	Uncertain	0.058	T;T;T;T
Polyphen		0.047	B;B;B;.
Vest4		0.11
MutPred		0.33		Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);.;.;
MVP		0.055
MPC		0.061
ClinPred		0.11	T
GERP RS		-0.51
Varity_R		0.11
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs41281692; hg19: chr7-120776097;