Variant 3-172710939-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020792.6(NCEH1):c.46G>A(p.Ala16Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0113 in 1,614,156 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 11 hom., cov: 33)

Exomes 𝑓: 0.012 ( 143 hom. )

Consequence

NCEH1
NM_020792.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.37

Variant links:

Genes affected

NCEH1 (HGNC:29260): (neutral cholesterol ester hydrolase 1) Predicted to enable hydrolase activity. Predicted to be involved in ether lipid metabolic process. Predicted to act upstream of or within SMAD protein signal transduction; protein dephosphorylation; and xenobiotic metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

NCEH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0087017715).

BP6

Variant 3-172710939-C-T is Benign according to our data. Variant chr3-172710939-C-T is described in ClinVar as [Benign]. Clinvar id is 780433.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCEH1	NM_020792.6 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	1/5	ENST00000475381.7
NCEH1	NM_001146276.3 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	1/5
NCEH1	NM_001146277.3 linkuse as main transcript	c.-344G>A		5_prime_UTR_variant	1/5
NCEH1	NM_001146278.3 linkuse as main transcript	c.-125G>A		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCEH1	ENST00000475381.7 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	1/5	1	NM_020792.6	P1	Q6PIU2-1

Frequencies

GnomAD3 genomes

AF:

0.00868

AC:

1322

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00896

AC:

2251

AN:

251132

Hom.:

AF XY:

0.00890

AC XY:

1209

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00378

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.0275

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.0115

AC:

16853

AN:

1461816

Hom.:

143

Cov.:

AF XY:

0.0112

AC XY:

8142

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00390

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.00959

GnomAD4 genome

AF:

0.00868

AC:

1322

AN:

152340

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

642

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0236

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00659

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0127

AC:

109

ExAC

AF:

0.00850

AC:

1032

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0087

T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

REVEL

Benign

0.20

Sift4G

Uncertain

0.052

T;T

Vest4

0.71

MVP

0.66

MPC

1.1

ClinPred

0.015

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over