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GeneBe

3-172648004-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020792.6(NCEH1):c.249C>T(p.Thr83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,094 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 33 hom. )

Consequence

NCEH1
NM_020792.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.67
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-172648004-G-A is Benign according to our data. Variant chr3-172648004-G-A is described in ClinVar as [Benign]. Clinvar id is 772866.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-7.67 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NCEH1NM_020792.6 linkuse as main transcriptc.249C>T p.Thr83= synonymous_variant 2/5 ENST00000475381.7
NCEH1NM_001146276.3 linkuse as main transcriptc.249C>T p.Thr83= synonymous_variant 2/5
NCEH1NM_001146277.3 linkuse as main transcriptc.-141C>T 5_prime_UTR_variant 2/5
NCEH1NM_001146278.3 linkuse as main transcriptc.-32-2312C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NCEH1ENST00000475381.7 linkuse as main transcriptc.249C>T p.Thr83= synonymous_variant 2/51 NM_020792.6 P1Q6PIU2-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00167
AC:
254
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000918
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0145
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00157
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.00277
AC:
695
AN:
251254
Hom.:
7
AF XY:
0.00351
AC XY:
476
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.00127
Gnomad ASJ exome
AF:
0.00219
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0130
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00175
Gnomad OTH exome
AF:
0.00244
GnomAD4 exome
AF:
0.00193
AC:
2826
AN:
1461894
Hom.:
33
Cov.:
34
AF XY:
0.00243
AC XY:
1765
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00102
Gnomad4 AMR exome
AF:
0.00134
Gnomad4 ASJ exome
AF:
0.00214
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0136
Gnomad4 FIN exome
AF:
0.000168
Gnomad4 NFE exome
AF:
0.00115
Gnomad4 OTH exome
AF:
0.00278
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00166
AC:
253
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.00196
AC XY:
146
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.000915
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0143
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.00157
Gnomad4 OTH
AF:
0.00285
Alfa
AF:
0.00187
Hom.:
0
Bravo
AF:
0.00147
Asia WGS
AF:
0.00462
AC:
16
AN:
3478
EpiCase
AF:
0.00316
EpiControl
AF:
0.00261

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 submitterclinical testingInvitaeJul 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
Cadd
Benign
0.0060
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs141870427; hg19: chr3-172365794; COSMIC: COSV99860550; API