19-50382924-C-T

Variant names:

• chr19-50382924-C-T
• rs1052677
• NM_007121.7:c.*322C>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.*322C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 119,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: NR1H2 NM_007121.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81
• Publications: 7 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=-0.93).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	NM_007121.7	MANE Select	c.*322C>T		3_prime_UTR	Exon 10 of 10	NP_009052.4	P55055-1
	NR1H2	NM_001256647.3		c.*322C>T		3_prime_UTR	Exon 9 of 9	NP_001243576.2	P55055-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	ENST00000253727.10	TSL:1 MANE Select	c.*322C>T		3_prime_UTR	Exon 10 of 10	ENSP00000253727.4	P55055-1
	NR1H2	ENST00000967772.1		c.*322C>T		3_prime_UTR	Exon 10 of 10	ENSP00000637831.1
	NR1H2	ENST00000593926.5	TSL:5	c.*322C>T		3_prime_UTR	Exon 9 of 9	ENSP00000471194.1	P55055-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000834 AC: 1 AN: 119976 Hom.: 0 Cov.: 0 AF XY: 0.0000167 AC XY: 1 AN XY: 59912

African (AFR) AF: 0.00 AC: 0 AN: 4136

American (AMR) AF: 0.00 AC: 0 AN: 4274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5060

East Asian (EAS) AF: 0.0000946 AC: 1 AN: 10568

South Asian (SAS) AF: 0.00 AC: 0 AN: 1590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 77574

Other (OTH) AF: 0.00 AC: 0 AN: 8512

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.011
DANN	Benign	0.48
PhyloP100		-3.8

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: rs1052677; hg19: chr19-50886181;