1-111159398-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_006090.5(CEPT1):c.358A>G(p.Ile120Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00985 in 1,612,082 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (5 hom., cov: 31)
  • Exomes 𝑓: 0.010 (96 hom.)
• Consequence: CEPT1 NM_006090.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.733

Genes affected

CEPT1 (HGNC:24289): (choline/ethanolamine phosphotransferase 1) This gene codes for a choline/ethanolaminephosphotransferase, which functions in the synthesis of choline- or ethanolamine- containing phospholipids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CEPT1
• BP4: Computational evidence support a benign effect (MetaRNN=0.0056552887).
• BP6: Variant 1-111159398-A-G is Benign according to our data. Variant chr1-111159398-A-G is described in ClinVar as [Benign]. Clinvar id is 775055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEPT1	NM_006090.5	c.358A>G	p.Ile120Val	missense_variant	3/9	ENST00000357172.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEPT1	ENST00000357172.9	c.358A>G	p.Ile120Val	missense_variant	3/9	1	NM_006090.5	P4

Frequencies

GnomAD3 genomes AF: 0.00809 AC: 1231 AN: 152142 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00731 AC: 1821 AN: 249064 Hom.: 16 AF XY: 0.00755 AC XY: 1017 AN XY: 134754

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00213

Gnomad ASJ exome AF: 0.00785

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00113

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.00796

GnomAD4 exome AF: 0.0100 AC: 14646 AN: 1459822 Hom.: 96 Cov.: 30 AF XY: 0.00987 AC XY: 7170 AN XY: 726254

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.00735

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000955

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.00910

GnomAD4 genome AF: 0.00808 AC: 1231 AN: 152260 Hom.: 5 Cov.: 31 AF XY: 0.00760 AC XY: 566 AN XY: 74456

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.0110 Hom.: 11

Bravo AF: 0.00669

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0117 AC: 45

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0126 AC: 108

ExAC AF: 0.00750 AC: 911

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0101

EpiControl AF: 0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	14
Dann	Benign	0.93
DEOGEN2	Benign	0.087	T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.72	T;.;T
MetaRNN	Benign	0.0057	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.060	N;N;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.69	N;N;.
REVEL	Benign	0.092
Sift	Benign	0.13	T;T;.
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.17
MVP		0.12
MPC		0.16
ClinPred		0.0032	T
GERP RS		-0.064
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs146158422; hg19: chr1-111702020; COSMIC: COSV99071238;