chr19-50375166-C-T

Variant names:

• chr19-50375166-C-T
• rs77094157
• ENST00000652203.1:c.-127-1553C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000652203.1(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 ENST00000652203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 2 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 -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652203.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	ENST00000652203.1		c.-127-1553C>T		intron	N/A	ENSP00000499121.1
	NR1H2	ENST00000600355.5	TSL:3	c.-127-1553C>T		intron	N/A	ENSP00000473099.1
	NR1H2	ENST00000593532.5	TSL:2	n.-469-1069C>T		intron	N/A	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

African (AFR) AF: 0.00157 AC: 58 AN: 36844

American (AMR) AF: 0.0102 AC: 153 AN: 14980

Ashkenazi Jewish (ASJ) AF: 0.0232 AC: 80 AN: 3448

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5138

South Asian (SAS) AF: 0.00951 AC: 45 AN: 4734

European-Finnish (FIN) AF: 0.0522 AC: 553 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00852 AC: 579 AN: 67956

Other (OTH) AF: 0.00638 AC: 13 AN: 2038

Alfa AF: 0.00443 Hom.: 3

Bravo AF: 0.00703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.92
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs77094157; hg19: chr19-50878423;