Genetic Variant 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:

Genome browser will be placed here

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr1-200048458-C-G

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