7-121136043-C-G

Variant names:

• chr7-121136043-C-G
• rs41281692
• NM_024913.5:c.1652C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024913.5(CPED1):​c.1652C>G​(p.Ala551Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,480,188 control chromosomes in the GnomAD database, including 156,829 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15347 hom., cov: 29)
  • Exomes 𝑓: 0.45 (141482 hom.)
• Consequence: CPED1 NM_024913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 30 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.1098183E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	NM_024913.5	MANE Select	c.1652C>G	p.Ala551Gly	missense	Exon 14 of 23	NP_079189.4
	CPED1	NM_001105533.1		c.1652C>G	p.Ala551Gly	missense	Exon 13 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.1652C>G	p.Ala551Gly	missense	Exon 14 of 23	ENSP00000309772.5	A4D0V7-1
	CPED1	ENST00000450913.6	TSL:1	c.1652C>G	p.Ala551Gly	missense	Exon 13 of 18	ENSP00000406122.2	A4D0V7-2
	CPED1	ENST00000423795.5	TSL:1	c.992C>G	p.Ala331Gly	missense	Exon 11 of 16	ENSP00000415573.1	G5E9U2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 64556 AN: 149568 Hom.: 15343 Cov.: 29

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.464

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.455

GnomAD2 exomes AF: 0.460 AC: 82685 AN: 179686 AF XY: 0.459

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.364

Gnomad EAS exome AF: 0.815

Gnomad FIN exome AF: 0.515

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.451 AC: 599981 AN: 1330512 Hom.: 141482 Cov.: 25 AF XY: 0.451 AC XY: 298003 AN XY: 660864

African (AFR) AF: 0.233 AC: 6658 AN: 28592

American (AMR) AF: 0.610 AC: 15817 AN: 25940

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 8678 AN: 23036

East Asian (EAS) AF: 0.842 AC: 28464 AN: 33800

South Asian (SAS) AF: 0.421 AC: 28256 AN: 67042

European-Finnish (FIN) AF: 0.512 AC: 25815 AN: 50446

Middle Eastern (MID) AF: 0.455 AC: 2383 AN: 5240

European-Non Finnish (NFE) AF: 0.440 AC: 458850 AN: 1041818

Other (OTH) AF: 0.459 AC: 25060 AN: 54598

GnomAD4 genome AF: 0.431 AC: 64568 AN: 149676 Hom.: 15347 Cov.: 29 AF XY: 0.441 AC XY: 32171 AN XY: 72982

African (AFR) AF: 0.255 AC: 10379 AN: 40658

American (AMR) AF: 0.597 AC: 8990 AN: 15062

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1284 AN: 3460

East Asian (EAS) AF: 0.845 AC: 4322 AN: 5114

South Asian (SAS) AF: 0.453 AC: 2154 AN: 4756

European-Finnish (FIN) AF: 0.531 AC: 5269 AN: 9926

Middle Eastern (MID) AF: 0.437 AC: 125 AN: 286

European-Non Finnish (NFE) AF: 0.453 AC: 30542 AN: 67430

Other (OTH) AF: 0.450 AC: 934 AN: 2074

Alfa AF: 0.448 Hom.: 11784

Bravo AF: 0.429

TwinsUK AF: 0.447 AC: 1657

ALSPAC AF: 0.450 AC: 1735

ESP6500AA AF: 0.258 AC: 1135

ESP6500EA AF: 0.441 AC: 3790

ExAC AF: 0.478 AC: 57656

Asia WGS AF: 0.573 AC: 1954 AN: 3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.88
DANN	Benign	0.67
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.58
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.0020
Sift	Benign	0.36	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.064
MPC		0.054
ClinPred		0.010	T
GERP RS		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.31
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs41281692; hg19: chr7-120776097; COSMIC: COSV59998258; COSMIC: COSV59998258;