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12-100503438-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000551379.5(NR1H4):c.51C>T(p.His17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,597,766 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 61 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 83 hom. )

Consequence

NR1H4
ENST00000551379.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.60
Variant links:
Genes affected
NR1H4 (HGNC:7967): (nuclear receptor subfamily 1 group H member 4) This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-100503438-C-T is Benign according to our data. Variant chr12-100503438-C-T is described in ClinVar as [Benign]. Clinvar id is 1224977.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=-1.6 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR1H4NM_001206979.2 linkuse as main transcriptc.80-7340C>T intron_variant ENST00000392986.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR1H4ENST00000392986.8 linkuse as main transcriptc.80-7340C>T intron_variant 1 NM_001206979.2 A1Q96RI1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0174
AC:
2651
AN:
152172
Hom.:
61
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0542
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.0122
Gnomad ASJ
AF:
0.0228
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00146
Gnomad OTH
AF:
0.0138
GnomAD3 exomes
AF:
0.00645
AC:
1474
AN:
228658
Hom.:
24
AF XY:
0.00556
AC XY:
703
AN XY:
126332
show subpopulations
Gnomad AFR exome
AF:
0.0548
Gnomad AMR exome
AF:
0.00673
Gnomad ASJ exome
AF:
0.0228
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000530
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00174
Gnomad OTH exome
AF:
0.00960
GnomAD4 exome
AF:
0.00315
AC:
4555
AN:
1445476
Hom.:
83
Cov.:
30
AF XY:
0.00302
AC XY:
2171
AN XY:
719410
show subpopulations
Gnomad4 AFR exome
AF:
0.0603
Gnomad4 AMR exome
AF:
0.00824
Gnomad4 ASJ exome
AF:
0.0219
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000429
Gnomad4 FIN exome
AF:
0.0000263
Gnomad4 NFE exome
AF:
0.000948
Gnomad4 OTH exome
AF:
0.00722
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0174
AC:
2656
AN:
152290
Hom.:
61
Cov.:
32
AF XY:
0.0166
AC XY:
1233
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0542
Gnomad4 AMR
AF:
0.0122
Gnomad4 ASJ
AF:
0.0228
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00146
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.0135
Hom.:
11
Bravo
AF:
0.0207
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00224
EpiControl
AF:
0.00262

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 testingGeneDxJun 20, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
0.61
Dann
Benign
0.56

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.

Other links and lift over

dbSNP: rs17030240; hg19: chr12-100897216; API