Genetic Variant NR5A2:c.1230+14C>T (chr1-200111335-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_205860.3(NR5A2):c.1230+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,202,218 control chromosomes in the GnomAD database, including 10,312 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 0.29 ( 2834 hom., cov: 14)

Exomes 𝑓: 0.24 ( 7478 hom. )

Consequence

NR5A2
NM_205860.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3 link	c.1230+14C>T		intron_variant	Intron 6 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NR5A2	ENST00000367362.8 link	c.1230+14C>T	intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7 link	c.1092+14C>T	intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5 link	c.1014+14C>T	intron_variant	Intron 5 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

23933

AN:

81952

Hom.:

2833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.0596

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.0128

Gnomad SAS

AF:

0.0703

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.356

AC:

45069

AN:

126484

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.337

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.240

AC:

269317

AN:

1120262

Hom.:

7478

Cov.:

AF XY:

0.241

AC XY:

133990

AN XY:

556416

show subpopulations

African (AFR)

AF:

0.415

AC:

10040

AN:

24184

American (AMR)

AF:

0.280

AC:

6856

AN:

24498

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

6244

AN:

18506

East Asian (EAS)

AF:

0.164

AC:

5071

AN:

30860

South Asian (SAS)

AF:

0.187

AC:

11399

AN:

61058

European-Finnish (FIN)

AF:

0.250

AC:

8742

AN:

35008

Middle Eastern (MID)

AF:

0.215

AC:

928

AN:

4324

European-Non Finnish (NFE)

AF:

0.238

AC:

208767

AN:

875598

Other (OTH)

AF:

0.244

AC:

11270

AN:

46226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

8591

17183

25774

34366

42957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7708

15416

23124

30832

38540

<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:

0.292

AC:

23941

AN:

81956

Hom.:

2834

Cov.:

AF XY:

0.281

AC XY:

11073

AN XY:

39358

show subpopulations

African (AFR)

AF:

0.471

AC:

12045

AN:

25586

American (AMR)

AF:

0.232

AC:

1602

AN:

6914

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

651

AN:

1946

East Asian (EAS)

AF:

0.0128

AC:

AN:

2582

South Asian (SAS)

AF:

0.0706

AC:

176

AN:

2492

European-Finnish (FIN)

AF:

0.174

AC:

811

AN:

4648

Middle Eastern (MID)

AF:

0.215

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.230

AC:

8271

AN:

36030

Other (OTH)

AF:

0.257

AC:

287

AN:

1116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

747

1494

2241

2988

3735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.450

Hom.:

16868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.6

(source)

DANN

Benign

0.58

PhyloP100

0.038

Mutation Taster

=100/0

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