7-121015831-C-A

Variant names:

• chr7-121015831-C-A
• rs137952014
• NM_024913.5:c.416C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024913.5(CPED1):​c.416C>A​(p.Pro139Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,405,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P139L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CPED1 NM_024913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042500883).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	NM_024913.5	MANE Select	c.416C>A	p.Pro139Gln	missense	Exon 3 of 23	NP_079189.4
	CPED1	NM_001105533.1		c.416C>A	p.Pro139Gln	missense	Exon 2 of 18	NP_001099003.1	Q9H6Q5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	ENST00000310396.10	TSL:1 MANE Select	c.416C>A	p.Pro139Gln	missense	Exon 3 of 23	ENSP00000309772.5	A4D0V7-1
	CPED1	ENST00000450913.6	TSL:1	c.416C>A	p.Pro139Gln	missense	Exon 2 of 18	ENSP00000406122.2	A4D0V7-2
	CPED1	ENST00000495036.5	TSL:1	n.863C>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1405688 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 696964

African (AFR) AF: 0.00 AC: 0 AN: 30272

American (AMR) AF: 0.00 AC: 0 AN: 31800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23962

East Asian (EAS) AF: 0.00 AC: 0 AN: 37284

South Asian (SAS) AF: 0.00 AC: 0 AN: 75546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090744

Other (OTH) AF: 0.00 AC: 0 AN: 58012

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.45
DANN	Benign	0.83
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.35
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.034
Sift	Benign	0.51	T
Sift4G	Benign	0.51	T
Polyphen		0.0020	B
Vest4		0.21
MutPred		0.34		Loss of loop (P = 0.0603)
MVP		0.030
MPC		0.057
ClinPred		0.028	T
GERP RS		0.42
Varity_R		0.021
gMVP		0.15
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs137952014; hg19: chr7-120655885;