chr19-50377797-G-A

Variant names:

• chr19-50377797-G-A
• rs55671147
• NM_007121.7:c.108G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_007121.7(NR1H2):​c.108G>A​(p.Glu36Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,610,756 control chromosomes in the GnomAD database, including 154 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 0.0087 (12 hom., cov: 32)
  • Exomes 𝑓: 0.014 (142 hom.)
• Consequence: NR1H2 NM_007121.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• Publications: 6 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=0.645 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00871 (1325/152206) while in subpopulation NFE AF = 0.0164 (1113/67984). AF 95% confidence interval is 0.0156. There are 12 homozygotes in GnomAd4. There are 553 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1325 AD gene.

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.108G>A	p.Glu36Glu	synonymous	Exon 4 of 10	NP_009052.4	P55055-1
	NR1H2	NM_001256647.3		c.108G>A	p.Glu36Glu	synonymous	Exon 4 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.108G>A	p.Glu36Glu	synonymous	Exon 4 of 10	ENSP00000253727.4	P55055-1
	NR1H2	ENST00000411902.6	TSL:1	c.108G>A	p.Glu36Glu	synonymous	Exon 4 of 9	ENSP00000396151.2	P55055-2
	NR1H2	ENST00000597157.1	TSL:1	c.108G>A	p.Glu36Glu	synonymous	Exon 2 of 4	ENSP00000469778.1	M0QYE6

Frequencies

GnomAD3 genomes AF: 0.00871 AC: 1325 AN: 152088 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00943 AC: 2309 AN: 244940 AF XY: 0.00962

Gnomad AFR exome AF: 0.00176

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.00133

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00469

Gnomad NFE exome AF: 0.0159

Gnomad OTH exome AF: 0.00933

GnomAD4 exome AF: 0.0142 AC: 20652 AN: 1458550 Hom.: 142 Cov.: 32 AF XY: 0.0140 AC XY: 10152 AN XY: 725594

African (AFR) AF: 0.00177 AC: 59 AN: 33308

American (AMR) AF: 0.00421 AC: 185 AN: 43988

Ashkenazi Jewish (ASJ) AF: 0.00143 AC: 37 AN: 25922

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.00672 AC: 578 AN: 85966

European-Finnish (FIN) AF: 0.00562 AC: 299 AN: 53222

Middle Eastern (MID) AF: 0.00400 AC: 23 AN: 5748

European-Non Finnish (NFE) AF: 0.0169 AC: 18755 AN: 1110522

Other (OTH) AF: 0.0119 AC: 715 AN: 60204

GnomAD4 genome AF: 0.00871 AC: 1325 AN: 152206 Hom.: 12 Cov.: 32 AF XY: 0.00743 AC XY: 553 AN XY: 74412

African (AFR) AF: 0.00238 AC: 99 AN: 41544

American (AMR) AF: 0.00314 AC: 48 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4822

European-Finnish (FIN) AF: 0.00283 AC: 30 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0164 AC: 1113 AN: 67984

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.0144 Hom.: 25

Bravo AF: 0.00863

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.6
DANN	Benign	0.89
PhyloP100		0.65
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=298/2	polymorphism

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: rs55671147; hg19: chr19-50881054; COSMIC: COSV99516635; COSMIC: COSV99516635;