rs28514894

Positions:

• chr19-50378069-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007121.7(NR1H2):​c.182-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,482,382 control chromosomes in the GnomAD database, including 85,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10410 hom., cov: 32)
  • Exomes 𝑓: 0.33 (75355 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.505

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-50378069-T-C is Benign according to our data. Variant chr19-50378069-T-C is described in ClinVar as [Benign]. Clinvar id is 1277347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H2	NM_007121.7	c.182-80T>C		intron_variant		ENST00000253727.10
NR1H2	NM_001256647.3	c.181+199T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H2	ENST00000253727.10	c.182-80T>C		intron_variant		1	NM_007121.7	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55159 AN: 151998 Hom.: 10392 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.333 AC: 442821 AN: 1330266 Hom.: 75355 Cov.: 23 AF XY: 0.334 AC XY: 218580 AN XY: 653904

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.363 AC: 55232 AN: 152116 Hom.: 10410 Cov.: 32 AF XY: 0.362 AC XY: 26895 AN XY: 74352

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.346

Alfa AF: 0.233 Hom.: 566

Bravo AF: 0.370

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

This variant is associated with the following publications: (PMID: 20939869) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs28514894; hg19: chr19-50881326; COSMIC: COSV53799804; COSMIC: COSV53799804;