rs2695121

Variant names:

• chr19-50377484-T-A
• rs2695121
• ENST00000597157.1:c.-122T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50377484-T-A
• chr19-50377484-T-C
• chr19-50377484-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000597157.1(NR1H2):​c.-122T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR1H2 ENST00000597157.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 42 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H2	NM_007121.7	c.-19-103T>A		intron_variant	Intron 2 of 9	ENST00000253727.10	NP_009052.4
NR1H2	NM_001256647.3	c.-19-103T>A		intron_variant	Intron 2 of 8		NP_001243576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10	c.-19-103T>A		intron_variant	Intron 2 of 9	1	NM_007121.7	ENSP00000253727.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151482 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 735430 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 380224

African (AFR) AF: 0.00 AC: 0 AN: 17024

American (AMR) AF: 0.00 AC: 0 AN: 24372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15672

East Asian (EAS) AF: 0.00 AC: 0 AN: 31826

South Asian (SAS) AF: 0.00 AC: 0 AN: 55178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 506272

Other (OTH) AF: 0.00 AC: 0 AN: 35266

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151482 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 73924

African (AFR) AF: 0.00 AC: 0 AN: 41190

American (AMR) AF: 0.00 AC: 0 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67852

Other (OTH) AF: 0.00 AC: 0 AN: 2084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.75
PhyloP100		-0.30
PromoterAI		-0.0060	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

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

Other links and lift over

dbSNP: rs2695121; hg19: chr19-50880741;