Genetic Variant NR5A2:c.1231-64C>T (chr1-200120744-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.1231-64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,445,166 control chromosomes in the GnomAD database, including 130,571 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 0.41 ( 13064 hom., cov: 33)

Exomes 𝑓: 0.42 ( 117507 hom. )

Consequence

NR5A2
NM_205860.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.154

Publications

4 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205860.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR5A2	NM_205860.3	MANE Select	c.1231-64C>T	intron	N/A	NP_995582.1	O00482-1
NR5A2	NM_003822.5		c.1093-64C>T	intron	N/A	NP_003813.1	F1D8R9
NR5A2	NM_001276464.2		c.1015-64C>T	intron	N/A	NP_001263393.1	O00482-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.1231-64C>T	intron	N/A	ENSP00000356331.3	O00482-1
NR5A2	ENST00000236914.7	TSL:1	c.1093-64C>T	intron	N/A	ENSP00000236914.3	O00482-2
NR5A2	ENST00000892175.1		c.1156-64C>T	intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62550

AN:

151906

Hom.:

13041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.414

GnomAD4 exome

AF:

0.424

AC:

548359

AN:

1293142

Hom.:

117507

AF XY:

0.422

AC XY:

267426

AN XY:

634096

show subpopulations

African (AFR)

AF:

0.368

AC:

9883

AN:

26868

American (AMR)

AF:

0.416

AC:

9737

AN:

23404

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

9467

AN:

18678

East Asian (EAS)

AF:

0.317

AC:

10981

AN:

34668

South Asian (SAS)

AF:

0.333

AC:

21096

AN:

63286

European-Finnish (FIN)

AF:

0.403

AC:

19604

AN:

48628

Middle Eastern (MID)

AF:

0.344

AC:

1763

AN:

5118

European-Non Finnish (NFE)

AF:

0.436

AC:

443924

AN:

1019322

Other (OTH)

AF:

0.412

AC:

21904

AN:

53170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

14642

29283

43925

58566

73208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13894

27788

41682

55576

69470

<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:

0.412

AC:

62606

AN:

152024

Hom.:

13064

Cov.:

AF XY:

0.408

AC XY:

30332

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.376

AC:

15590

AN:

41454

American (AMR)

AF:

0.441

AC:

6739

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1780

AN:

3470

East Asian (EAS)

AF:

0.296

AC:

1527

AN:

5162

South Asian (SAS)

AF:

0.347

AC:

1677

AN:

4826

European-Finnish (FIN)

AF:

0.393

AC:

4150

AN:

10564

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.440

AC:

29888

AN:

67974

Other (OTH)

AF:

0.409

AC:

864

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1944

3889

5833

7778

9722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.389

Hom.:

4114

Bravo

AF:

0.411

Asia WGS

AF:

0.362

AC:

1260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.8

(source)

DANN

Benign

0.36

PhyloP100

-0.15

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over