19-50382924-C-G

Variant names:

• chr19-50382924-C-G
• rs1052677
• NM_007121.7:c.*322C>G

Variant summary

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

The NM_007121.7(NR1H2):​c.*322C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 158,234 control chromosomes in the GnomAD database, including 1,769 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 0.45 (1109 hom., cov: 34)
  • Exomes 𝑓: 0.096 (660 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

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>G		3_prime_UTR	Exon 10 of 10	NP_009052.4	P55055-1
	NR1H2	NM_001256647.3		c.*322C>G		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>G		3_prime_UTR	Exon 10 of 10	ENSP00000253727.4	P55055-1
	NR1H2	ENST00000967772.1		c.*322C>G		3_prime_UTR	Exon 10 of 10	ENSP00000637831.1
	NR1H2	ENST00000593926.5	TSL:5	c.*322C>G		3_prime_UTR	Exon 9 of 9	ENSP00000471194.1	P55055-1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 17251 AN: 38486 Hom.: 1112 Cov.: 34

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.0959 AC: 11483 AN: 119734 Hom.: 660 Cov.: 0 AF XY: 0.0969 AC XY: 5792 AN XY: 59790

African (AFR) AF: 0.137 AC: 566 AN: 4120

American (AMR) AF: 0.0866 AC: 369 AN: 4260

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 796 AN: 5046

East Asian (EAS) AF: 0.166 AC: 1749 AN: 10536

South Asian (SAS) AF: 0.172 AC: 273 AN: 1584

European-Finnish (FIN) AF: 0.0436 AC: 331 AN: 7592

Middle Eastern (MID) AF: 0.150 AC: 98 AN: 654

European-Non Finnish (NFE) AF: 0.0834 AC: 6455 AN: 77436

Other (OTH) AF: 0.0995 AC: 846 AN: 8506

GnomAD4 genome AF: 0.448 AC: 17250 AN: 38500 Hom.: 1109 Cov.: 34 AF XY: 0.453 AC XY: 8321 AN XY: 18358

African (AFR) AF: 0.496 AC: 6461 AN: 13022

American (AMR) AF: 0.448 AC: 1595 AN: 3558

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 604 AN: 1274

East Asian (EAS) AF: 0.466 AC: 791 AN: 1698

South Asian (SAS) AF: 0.521 AC: 978 AN: 1876

European-Finnish (FIN) AF: 0.362 AC: 468 AN: 1292

Middle Eastern (MID) AF: 0.500 AC: 45 AN: 90

European-Non Finnish (NFE) AF: 0.398 AC: 5907 AN: 14848

Other (OTH) AF: 0.477 AC: 264 AN: 554

Alfa AF: 0.110 Hom.: 81

Bravo AF: 0.119

Asia WGS AF: 0.176 AC: 599 AN: 3410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0070
DANN	Benign	0.29
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV53799824; COSMIC: COSV53799824;