NM_007121.7:c.927+124A>G

Variant names:

• chr19-50379305-A-G
• rs78105260
• NM_007121.7:c.927+124A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007121.7(NR1H2):​c.927+124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,082,804 control chromosomes in the GnomAD database, including 89 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 0.0091 (13 hom., cov: 33)
  • Exomes 𝑓: 0.010 (76 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 1 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=-0.81).
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0103 (9630/930456) while in subpopulation MID AF = 0.0233 (103/4414). AF 95% confidence interval is 0.0197. There are 76 homozygotes in GnomAdExome4. There are 4718 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1392 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	NM_007121.7	MANE Select	c.927+124A>G		intron	N/A	NP_009052.4
	NR1H2	NM_001256647.3		c.636+124A>G		intron	N/A	NP_001243576.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	ENST00000253727.10	TSL:1 MANE Select	c.927+124A>G		intron	N/A	ENSP00000253727.4
	NR1H2	ENST00000411902.6	TSL:1	c.636+124A>G		intron	N/A	ENSP00000396151.2
	NR1H2	ENST00000593926.5	TSL:5	c.927+124A>G		intron	N/A	ENSP00000471194.1

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1394 AN: 152230 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0103 AC: 9630 AN: 930456 Hom.: 76 AF XY: 0.0101 AC XY: 4718 AN XY: 466424

African (AFR) AF: 0.00157 AC: 34 AN: 21692

American (AMR) AF: 0.00994 AC: 208 AN: 20918

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 763 AN: 16654

East Asian (EAS) AF: 0.0000291 AC: 1 AN: 34406

South Asian (SAS) AF: 0.00240 AC: 138 AN: 57598

European-Finnish (FIN) AF: 0.0117 AC: 399 AN: 34130

Middle Eastern (MID) AF: 0.0233 AC: 103 AN: 4414

European-Non Finnish (NFE) AF: 0.0108 AC: 7537 AN: 698920

Other (OTH) AF: 0.0107 AC: 447 AN: 41724

GnomAD4 genome AF: 0.00914 AC: 1392 AN: 152348 Hom.: 13 Cov.: 33 AF XY: 0.00873 AC XY: 650 AN XY: 74498

African (AFR) AF: 0.00212 AC: 88 AN: 41588

American (AMR) AF: 0.0117 AC: 179 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.00772 AC: 82 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 811 AN: 68024

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0102 Hom.: 0

Bravo AF: 0.00899

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.89
DANN	Benign	0.72
PhyloP100		-0.018
Mutation Taster		=100/0	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: rs78105260; hg19: chr19-50882562;