19-50378069-T-C

Variant names:

• chr19-50378069-T-C
• rs28514894
• NM_007121.7:c.182-80T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007121.7(NR1H2):​c.182-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,482,382 control chromosomes in the GnomAD database, including 85,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10410 hom., cov: 32)
  • Exomes 𝑓: 0.33 (75355 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.505
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-50378069-T-C is Benign according to our data. Variant chr19-50378069-T-C is described in ClinVar as Benign. ClinVar VariationId is 1277347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 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.182-80T>C		intron	N/A	NP_009052.4
	NR1H2	NM_001256647.3		c.181+199T>C		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.182-80T>C		intron	N/A	ENSP00000253727.4
	NR1H2	ENST00000411902.6	TSL:1	c.181+199T>C		intron	N/A	ENSP00000396151.2
	NR1H2	ENST00000597157.1	TSL:1	c.182-80T>C		intron	N/A	ENSP00000469778.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55159 AN: 151998 Hom.: 10392 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.333 AC: 442821 AN: 1330266 Hom.: 75355 Cov.: 23 AF XY: 0.334 AC XY: 218580 AN XY: 653904

African (AFR) AF: 0.445 AC: 13220 AN: 29682

American (AMR) AF: 0.450 AC: 13920 AN: 30946

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 7889 AN: 20370

East Asian (EAS) AF: 0.166 AC: 6426 AN: 38596

South Asian (SAS) AF: 0.383 AC: 26951 AN: 70414

European-Finnish (FIN) AF: 0.302 AC: 13575 AN: 44924

Middle Eastern (MID) AF: 0.381 AC: 1603 AN: 4204

European-Non Finnish (NFE) AF: 0.329 AC: 340934 AN: 1036082

Other (OTH) AF: 0.332 AC: 18303 AN: 55048

GnomAD4 genome AF: 0.363 AC: 55232 AN: 152116 Hom.: 10410 Cov.: 32 AF XY: 0.362 AC XY: 26895 AN XY: 74352

African (AFR) AF: 0.441 AC: 18284 AN: 41454

American (AMR) AF: 0.409 AC: 6261 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.159 AC: 822 AN: 5184

South Asian (SAS) AF: 0.385 AC: 1856 AN: 4822

European-Finnish (FIN) AF: 0.295 AC: 3116 AN: 10580

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22354 AN: 67994

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.338 Hom.: 1945

Bravo AF: 0.370

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.41
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28514894; hg19: chr19-50881326; COSMIC: COSV53799804; COSMIC: COSV53799804;