19-50378912-A-T

Variant names:

• chr19-50378912-A-T
• rs2248949
• NM_007121.7:c.748-90A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007121.7(NR1H2):​c.748-90A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 19 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007121.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	NM_007121.7	MANE Select	c.748-90A>T		intron	N/A	NP_009052.4
	NR1H2	NM_001256647.3		c.457-90A>T		intron	N/A	NP_001243576.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	ENST00000253727.10	TSL:1 MANE Select	c.748-90A>T		intron	N/A	ENSP00000253727.4
	NR1H2	ENST00000411902.6	TSL:1	c.457-90A>T		intron	N/A	ENSP00000396151.2
	NR1H2	ENST00000597085.1	TSL:3	n.172A>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1392966 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 685922

African (AFR) AF: 0.00 AC: 0 AN: 31760

American (AMR) AF: 0.00 AC: 0 AN: 38076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39150

South Asian (SAS) AF: 0.00 AC: 0 AN: 75680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075356

Other (OTH) AF: 0.00 AC: 0 AN: 57346

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 36913

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.52
PhyloP100		0.099

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: rs2248949; hg19: chr19-50882169;