chr19-50375166-C-T

Position:

• chr19-50375166-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000600355.5(NR1H2):​c.-127-1553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 146,936 control chromosomes in the GnomAD database, including 24 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 0.010 (24 hom., cov: 32)
• Consequence: NR1H2 ENST00000600355.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 1491 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.50375166C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000652203.1	c.-127-1553C>T		intron_variant				ENSP00000499121.1
NR1H2	ENST00000600355.5	c.-127-1553C>T		intron_variant		3		ENSP00000473099.1
NR1H2	ENST00000593532.5	n.-469-1069C>T		intron_variant		2		ENSP00000472271.1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1491 AN: 146840 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00158

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0232

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00992

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00852

Gnomad OTH AF: 0.00645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0101 AC: 1491 AN: 146936 Hom.: 24 Cov.: 32 AF XY: 0.0121 AC XY: 871 AN XY: 71908

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.0232

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.00951

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.00852

Gnomad4 OTH AF: 0.00638

Alfa AF: 0.00749 Hom.: 3

Bravo AF: 0.00703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77094157; hg19: chr19-50878423;