Genetic Variant NM_205860.3:c.1569C>T (chr1-200174153-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_205860.3(NR5A2):c.1569C>T(p.Asn523Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,612,438 control chromosomes in the GnomAD database, including 74,786 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 0.32 ( 8011 hom., cov: 28)

Exomes 𝑓: 0.30 ( 66775 hom. )

Consequence

NR5A2
NM_205860.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Publications

22 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-2.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3 link	c.1569C>T	p.Asn523Asn	synonymous_variant	Exon 8 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.1569C>T	p.Asn523Asn	synonymous_variant	Exon 8 of 8	1	NM_205860.3	ENSP00000356331.3	O00482-1
NR5A2	ENST00000236914.7 link	c.1431C>T	p.Asn477Asn	synonymous_variant	Exon 7 of 7	1		ENSP00000236914.3	O00482-2
NR5A2	ENST00000544748.5 link	c.1353C>T	p.Asn451Asn	synonymous_variant	Exon 7 of 7	2		ENSP00000439116.1	O00482-4

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48562

AN:

151248

Hom.:

7996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.296

GnomAD2 exomes

AF:

0.320

AC:

80120

AN:

250526

AF XY:

0.313

show subpopulations

Gnomad AFR exome

AF:

0.351

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.534

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.299

AC:

436393

AN:

1461072

Hom.:

66775

Cov.:

AF XY:

0.297

AC XY:

215827

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.351

AC:

11731

AN:

33452

American (AMR)

AF:

0.356

AC:

15880

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7619

AN:

26102

East Asian (EAS)

AF:

0.524

AC:

20771

AN:

39660

South Asian (SAS)

AF:

0.251

AC:

21648

AN:

86166

European-Finnish (FIN)

AF:

0.292

AC:

15582

AN:

53386

Middle Eastern (MID)

AF:

0.287

AC:

1653

AN:

5766

European-Non Finnish (NFE)

AF:

0.291

AC:

323424

AN:

1111566

Other (OTH)

AF:

0.300

AC:

18085

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

16639

33277

49916

66554

83193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10854

21708

32562

43416

54270

<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:

0.321

AC:

48608

AN:

151366

Hom.:

8011

Cov.:

AF XY:

0.323

AC XY:

23910

AN XY:

73942

show subpopulations

African (AFR)

AF:

0.352

AC:

14481

AN:

41178

American (AMR)

AF:

0.351

AC:

5340

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

999

AN:

3468

East Asian (EAS)

AF:

0.522

AC:

2670

AN:

5116

South Asian (SAS)

AF:

0.266

AC:

1276

AN:

4792

European-Finnish (FIN)

AF:

0.286

AC:

2993

AN:

10448

Middle Eastern (MID)

AF:

0.317

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.291

AC:

19738

AN:

67838

Other (OTH)

AF:

0.299

AC:

627

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1635

3270

4904

6539

8174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.301

Hom.:

11069

Bravo

AF:

0.330

Asia WGS

AF:

0.380

AC:

1320

AN:

3478

EpiCase

AF:

0.287

EpiControl

AF:

0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.029

(source)

DANN

Benign

0.66

PhyloP100

-2.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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