dbSNP rs2303045: NR1H2:c.928-119G>A (chr19-50379661-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007121.7(NR1H2):c.928-119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000591 in 693,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

NR1H2
NM_007121.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.636

Publications

9 publications found

Variant links:

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]

NR1H2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H2	NM_007121.7 link	c.928-119G>A		intron_variant	Intron 7 of 9	ENST00000253727.10	NP_009052.4	P55055-1F1D8P7
NR1H2	NM_001256647.3 link	c.637-119G>A		intron_variant	Intron 6 of 8		NP_001243576.2	P55055-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10 link	c.928-119G>A		intron_variant	Intron 7 of 9	1	NM_007121.7	ENSP00000253727.4		P55055-1

Frequencies

GnomAD3 genomes

AF:

0.0000468

AC:

AN:

149442

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000625

AC:

AN:

544220

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

290390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15940

American (AMR)

AF:

0.000180

AC:

AN:

33402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18044

East Asian (EAS)

AF:

0.00

AC:

AN:

32144

South Asian (SAS)

AF:

0.00

AC:

AN:

59090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3894

European-Non Finnish (NFE)

AF:

0.0000763

AC:

AN:

314370

Other (OTH)

AF:

0.000133

AC:

AN:

30106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000468

AC:

AN:

149550

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73108

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39302

American (AMR)

AF:

0.0000660

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67902

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.8

(source)

DANN

Benign

0.47

PhyloP100

-0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over