rs12972221

Variant names:

• chr19-50375883-G-T
• rs12972221
• ENST00000652203.1:c.-127-836G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000652203.1	c.-127-836G>T		intron_variant	Intron 2 of 10			ENSP00000499121.1
NR1H2	ENST00000600355.5	c.-127-836G>T		intron_variant	Intron 2 of 4	3		ENSP00000473099.1
NR1H2	ENST00000593532.5	n.-469-352G>T		intron_variant	Intron 4 of 13	2		ENSP00000472271.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44618 AN: 151892 Hom.: 6921 Cov.: 33

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

African (AFR) AF: 0.206 AC: 8526 AN: 41432

American (AMR) AF: 0.378 AC: 5783 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3468

East Asian (EAS) AF: 0.162 AC: 839 AN: 5168

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4818

European-Finnish (FIN) AF: 0.296 AC: 3123 AN: 10542

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22225 AN: 67988

Other (OTH) AF: 0.298 AC: 625 AN: 2098

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
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12972221; hg19: chr19-50879140;