chr7-121261641-G-A

Variant names:

• chr7-121261641-G-A
• rs10953934
• ENST00000450913.6:c.2320G>A

Variant summary

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

The NM_001105533.1(CPED1):​c.2320G>A​(p.Asp774Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,609,100 control chromosomes in the GnomAD database, including 116,955 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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 0.40 (12553 hom., cov: 31)
  • Exomes 𝑓: 0.37 (104402 hom.)
• Consequence: CPED1 NM_001105533.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• 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]

LOC124901735 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.02728285E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105533.1. 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.2311-4586G>A		intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.2320G>A	p.Asp774Asn	missense	Exon 18 of 18	NP_001099003.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	ENST00000450913.6	TSL:1	c.2320G>A	p.Asp774Asn	missense	Exon 18 of 18	ENSP00000406122.2
	CPED1	ENST00000423795.5	TSL:1	c.1660G>A	p.Asp554Asn	missense	Exon 16 of 16	ENSP00000415573.1
	CPED1	ENST00000310396.10	TSL:1 MANE Select	c.2311-4586G>A		intron	N/A	ENSP00000309772.5

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60042 AN: 151560 Hom.: 12519 Cov.: 31

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.396

GnomAD2 exomes AF: 0.350 AC: 84599 AN: 241372 AF XY: 0.355

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.374 AC: 545503 AN: 1457420 Hom.: 104402 Cov.: 41 AF XY: 0.375 AC XY: 271466 AN XY: 724656

African (AFR) AF: 0.501 AC: 16713 AN: 33346

American (AMR) AF: 0.238 AC: 10507 AN: 44196

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11653 AN: 26014

East Asian (EAS) AF: 0.117 AC: 4621 AN: 39492

South Asian (SAS) AF: 0.373 AC: 31930 AN: 85576

European-Finnish (FIN) AF: 0.366 AC: 19465 AN: 53134

Middle Eastern (MID) AF: 0.424 AC: 2439 AN: 5748

European-Non Finnish (NFE) AF: 0.383 AC: 425223 AN: 1109766

Other (OTH) AF: 0.382 AC: 22952 AN: 60148

GnomAD4 genome AF: 0.396 AC: 60138 AN: 151680 Hom.: 12553 Cov.: 31 AF XY: 0.391 AC XY: 29006 AN XY: 74096

African (AFR) AF: 0.500 AC: 20663 AN: 41350

American (AMR) AF: 0.303 AC: 4613 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1591 AN: 3462

East Asian (EAS) AF: 0.127 AC: 651 AN: 5122

South Asian (SAS) AF: 0.356 AC: 1714 AN: 4814

European-Finnish (FIN) AF: 0.363 AC: 3830 AN: 10538

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25835 AN: 67856

Other (OTH) AF: 0.404 AC: 851 AN: 2106

Alfa AF: 0.389 Hom.: 18883

Bravo AF: 0.396

TwinsUK AF: 0.369 AC: 1370

ALSPAC AF: 0.382 AC: 1474

ESP6500AA AF: 0.493 AC: 1858

ESP6500EA AF: 0.389 AC: 3188

ExAC AF: 0.353 AC: 42612

Asia WGS AF: 0.309 AC: 1075 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.30
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00012	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.00010	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.45
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.16
ClinPred		0.013	T
GERP RS		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10953934; hg19: chr7-120901695; COSMIC: COSV60003977;