NM_007121.7:c.1028-22C>T

Variant names:

• chr19-50381944-C-T
• rs2303044
• NM_007121.7:c.1028-22C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007121.7(NR1H2):​c.1028-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,536,420 control chromosomes in the GnomAD database, including 5,970 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 0.086 (661 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5309 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 15 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

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.1028-22C>T		intron	N/A	NP_009052.4
	NR1H2	NM_001256647.3		c.737-22C>T		intron	N/A	NP_001243576.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	ENST00000253727.10	TSL:1 MANE Select	c.1028-22C>T		intron	N/A	ENSP00000253727.4
	NR1H2	ENST00000411902.6	TSL:1	c.737-22C>T		intron	N/A	ENSP00000396151.2
	NR1H2	ENST00000967772.1		c.1093C>T	p.Arg365Trp	missense	Exon 9 of 10	ENSP00000637831.1

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13142 AN: 152124 Hom.: 661 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0885

GnomAD2 exomes AF: 0.0993 AC: 14400 AN: 145042 AF XY: 0.104

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.0360

Gnomad NFE exome AF: 0.0759

Gnomad OTH exome AF: 0.0958

GnomAD4 exome AF: 0.0816 AC: 112981 AN: 1384178 Hom.: 5309 Cov.: 31 AF XY: 0.0847 AC XY: 57718 AN XY: 681120

African (AFR) AF: 0.113 AC: 3565 AN: 31428

American (AMR) AF: 0.0898 AC: 3139 AN: 34938

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3494 AN: 24300

East Asian (EAS) AF: 0.159 AC: 5670 AN: 35654

South Asian (SAS) AF: 0.170 AC: 13166 AN: 77636

European-Finnish (FIN) AF: 0.0362 AC: 1748 AN: 48238

Middle Eastern (MID) AF: 0.137 AC: 728 AN: 5328

European-Non Finnish (NFE) AF: 0.0715 AC: 76417 AN: 1069286

Other (OTH) AF: 0.0881 AC: 5054 AN: 57370

GnomAD4 genome AF: 0.0863 AC: 13136 AN: 152242 Hom.: 661 Cov.: 33 AF XY: 0.0855 AC XY: 6369 AN XY: 74454

African (AFR) AF: 0.112 AC: 4653 AN: 41546

American (AMR) AF: 0.0784 AC: 1200 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3470

East Asian (EAS) AF: 0.144 AC: 743 AN: 5162

South Asian (SAS) AF: 0.172 AC: 833 AN: 4830

European-Finnish (FIN) AF: 0.0324 AC: 344 AN: 10620

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0680 AC: 4622 AN: 68002

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.0835 Hom.: 145

Bravo AF: 0.0903

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.046
DANN	Benign	0.86
PhyloP100		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2303044; hg19: chr19-50885201; COSMIC: COSV53801972; COSMIC: COSV53801972;