dbSNP rs2821368: NR5A2:p.Pro250Pro (chr1-200048458-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7BA1

The NM_205860.3(NR5A2):c.750C>G(p.Pro250Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,613,982 control chromosomes in the GnomAD database, including 32,724 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 6860 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25864 hom. )

Consequence

NR5A2
NM_205860.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950

Publications

13 publications found

Variant links:

Genes affected

NR5A2 (HGNC:7984): (nuclear receptor subfamily 5 group A member 2) The protein encoded by this gene is a DNA-binding zinc finger transcription factor and is a member of the fushi tarazu factor-1 subfamily of orphan nuclear receptors. The encoded protein is involved in the expression of genes for hepatitis B virus and cholesterol biosynthesis, and may be an important regulator of embryonic development. [provided by RefSeq, Jun 2016]

NR5A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP7

Synonymous conserved (PhyloP=-0.095 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3 link	c.750C>G	p.Pro250Pro	synonymous_variant	Exon 5 of 8	ENST00000367362.8	NP_995582.1	O00482-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NR5A2	ENST00000367362.8 link	c.750C>G	p.Pro250Pro	synonymous_variant	Exon 5 of 8	1	NM_205860.3	ENSP00000356331.3	O00482-1
NR5A2	ENST00000236914.7 link	c.612C>G	p.Pro204Pro	synonymous_variant	Exon 4 of 7	1		ENSP00000236914.3	O00482-2
NR5A2	ENST00000367357.3 link	c.510C>G	p.Pro170Pro	synonymous_variant	Exon 3 of 4	1		ENSP00000356326.3	H0Y328
NR5A2	ENST00000544748.5 link	c.534C>G	p.Pro178Pro	synonymous_variant	Exon 4 of 7	2		ENSP00000439116.1	O00482-4

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39604

AN:

152000

Hom.:

6845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.0410

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.321

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.258

GnomAD2 exomes

AF:

0.183

AC:

46071

AN:

251412

AF XY:

0.178

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.0370

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.176

AC:

257721

AN:

1461864

Hom.:

25864

Cov.:

AF XY:

0.175

AC XY:

127097

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.521

AC:

17429

AN:

33480

American (AMR)

AF:

0.140

AC:

6259

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7630

AN:

26136

East Asian (EAS)

AF:

0.0282

AC:

1121

AN:

39700

South Asian (SAS)

AF:

0.139

AC:

11974

AN:

86258

European-Finnish (FIN)

AF:

0.195

AC:

10441

AN:

53408

Middle Eastern (MID)

AF:

0.253

AC:

1462

AN:

5768

European-Non Finnish (NFE)

AF:

0.171

AC:

189832

AN:

1111994

Other (OTH)

AF:

0.192

AC:

11573

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13844

27687

41531

55374

69218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.261

AC:

39657

AN:

152118

Hom.:

6860

Cov.:

AF XY:

0.258

AC XY:

19167

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.492

AC:

20384

AN:

41468

American (AMR)

AF:

0.199

AC:

3032

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1003

AN:

3470

East Asian (EAS)

AF:

0.0409

AC:

212

AN:

5186

South Asian (SAS)

AF:

0.126

AC:

608

AN:

4822

European-Finnish (FIN)

AF:

0.197

AC:

2081

AN:

10582

Middle Eastern (MID)

AF:

0.310

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.171

AC:

11614

AN:

68006

Other (OTH)

AF:

0.254

AC:

535

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1363

2726

4090

5453

6816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.206

Hom.:

1227

Bravo

AF:

0.274

Asia WGS

AF:

0.105

AC:

365

AN:

3478

EpiCase

AF:

0.183

EpiControl

AF:

0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.0

(source)

DANN

Benign

0.70

PhyloP100

-0.095

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

Publications

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rs2821368

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