7-121261641-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105533.1(CPED1):​c.2320G>C​(p.Asp774His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078881115).

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>C		intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.2320G>C	p.Asp774His	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>C	p.Asp774His	missense	Exon 18 of 18	ENSP00000406122.2
	CPED1	ENST00000423795.5	TSL:1	c.1660G>C	p.Asp554His	missense	Exon 16 of 16	ENSP00000415573.1
	CPED1	ENST00000310396.10	TSL:1 MANE Select	c.2311-4586G>C		intron	N/A	ENSP00000309772.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241372 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457862 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 724902

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110036

Other (OTH) AF: 0.00 AC: 0 AN: 60160

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.68
DANN	Benign	0.43
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.45
PROVEAN	Benign	0.52	N
REVEL	Benign	0.0050
Sift	Pathogenic	0.0	D
Polyphen		0.37	B
Vest4		0.21
MutPred		0.42		Gain of sheet (P = 0.0125)
MVP		0.055
ClinPred		0.086	T
GERP RS		1.9
Mutation Taster		=100/0	polymorphism

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;