rs41432149

Variant names:

• chr19-50378915-C-T
• rs41432149
• NM_007121.7:c.748-87C>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.748-87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,545,210 control chromosomes in the GnomAD database, including 82,696 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 0.29 (6944 hom., cov: 32)
  • Exomes 𝑓: 0.33 (75752 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 11 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 (AMR) allele frequency at 95% confidence interval = 0.371 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.748-87C>T		intron	N/A	NP_009052.4	P55055-1
	NR1H2	NM_001256647.3		c.457-87C>T		intron	N/A	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.748-87C>T		intron	N/A	ENSP00000253727.4	P55055-1
	NR1H2	ENST00000411902.6	TSL:1	c.457-87C>T		intron	N/A	ENSP00000396151.2	P55055-2
	NR1H2	ENST00000967772.1		c.748-87C>T		intron	N/A	ENSP00000637831.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44743 AN: 151852 Hom.: 6942 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.326 AC: 454267 AN: 1393240 Hom.: 75752 Cov.: 31 AF XY: 0.328 AC XY: 224923 AN XY: 686190

African (AFR) AF: 0.203 AC: 6467 AN: 31854

American (AMR) AF: 0.438 AC: 16741 AN: 38214

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 8284 AN: 21726

East Asian (EAS) AF: 0.169 AC: 6629 AN: 39168

South Asian (SAS) AF: 0.367 AC: 27789 AN: 75790

European-Finnish (FIN) AF: 0.305 AC: 14776 AN: 48478

Middle Eastern (MID) AF: 0.375 AC: 2009 AN: 5364

European-Non Finnish (NFE) AF: 0.329 AC: 353556 AN: 1075274

Other (OTH) AF: 0.314 AC: 18016 AN: 57372

GnomAD4 genome AF: 0.295 AC: 44764 AN: 151970 Hom.: 6944 Cov.: 32 AF XY: 0.295 AC XY: 21917 AN XY: 74292

African (AFR) AF: 0.206 AC: 8560 AN: 41496

American (AMR) AF: 0.379 AC: 5786 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3466

East Asian (EAS) AF: 0.161 AC: 834 AN: 5178

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4810

European-Finnish (FIN) AF: 0.295 AC: 3105 AN: 10540

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22308 AN: 67908

Other (OTH) AF: 0.298 AC: 629 AN: 2108

Alfa AF: 0.311 Hom.: 952

Bravo AF: 0.293

Asia WGS AF: 0.251 AC: 872 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	2.0
DANN	Benign	0.68
PhyloP100		-0.19
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41432149;

hg19: chr19-50882172;

COSMIC: COSV53801117;

COSMIC: COSV53801117;