rs12972221

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000652203.1(NR1H2):​c.-127-836G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,000 control chromosomes in the GnomAD database, including 6,923 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6923 hom., cov: 33)

Consequence

NR1H2
ENST00000652203.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.243
Variant links:
Genes affected
NR1H2 (HGNC:7965): (nuclear receptor subfamily 1 group H member 2) The liver X receptors, LXRA (NR1H3; MIM 602423) and LXRB, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. The inducible LXRA is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRB is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs; see MIM 180245) and regulate expression of target genes containing LXR response elements (summary by Korf et al., 2009 [PubMed 19436111]).[supplied by OMIM, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NR1H2ENST00000600355.5 linkuse as main transcriptc.-127-836G>T intron_variant 3 ENSP00000473099
NR1H2ENST00000652203.1 linkuse as main transcriptc.-127-836G>T intron_variant ENSP00000499121 P1P55055-1
NR1H2ENST00000593532.5 linkuse as main transcriptc.-469-352G>T intron_variant, NMD_transcript_variant 2 ENSP00000472271

Frequencies

GnomAD3 genomes
AF:
0.294
AC:
44618
AN:
151892
Hom.:
6921
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.206
Gnomad AMI
AF:
0.378
Gnomad AMR
AF:
0.378
Gnomad ASJ
AF:
0.387
Gnomad EAS
AF:
0.162
Gnomad SAS
AF:
0.358
Gnomad FIN
AF:
0.296
Gnomad MID
AF:
0.348
Gnomad NFE
AF:
0.327
Gnomad OTH
AF:
0.301
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.294
AC:
44640
AN:
152000
Hom.:
6923
Cov.:
33
AF XY:
0.294
AC XY:
21849
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.206
Gnomad4 AMR
AF:
0.378
Gnomad4 ASJ
AF:
0.387
Gnomad4 EAS
AF:
0.162
Gnomad4 SAS
AF:
0.359
Gnomad4 FIN
AF:
0.296
Gnomad4 NFE
AF:
0.327
Gnomad4 OTH
AF:
0.298
Alfa
AF:
0.310
Hom.:
945
Bravo
AF:
0.292
Asia WGS
AF:
0.249
AC:
866
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.4
DANN
Benign
0.70

Splicing

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: rs12972221; hg19: chr19-50879140; API