Genetic Variant NR5A2:c.1378+136C>T (chr1-200121091-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.1378+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 887,526 control chromosomes in the GnomAD database, including 75,710 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 ( 13074 hom., cov: 33)

Exomes 𝑓: 0.41 ( 62636 hom. )

Consequence

NR5A2
NM_205860.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.574

Publications

11 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=-0.81).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3 link	c.1378+136C>T		intron_variant	Intron 7 of 7	ENST00000367362.8	NP_995582.1	O00482-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NR5A2	ENST00000367362.8 link	c.1378+136C>T	intron_variant	Intron 7 of 7	1	NM_205860.3	ENSP00000356331.3	O00482-1
NR5A2	ENST00000236914.7 link	c.1240+136C>T	intron_variant	Intron 6 of 6	1		ENSP00000236914.3	O00482-2
NR5A2	ENST00000544748.5 link	c.1162+136C>T	intron_variant	Intron 6 of 6	2		ENSP00000439116.1	O00482-4

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62592

AN:

151930

Hom.:

13051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.414

GnomAD4 exome

AF:

0.410

AC:

301449

AN:

735478

Hom.:

62636

AF XY:

0.408

AC XY:

156471

AN XY:

383434

show subpopulations

African (AFR)

AF:

0.371

AC:

6541

AN:

17652

American (AMR)

AF:

0.414

AC:

10700

AN:

25844

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

8298

AN:

16480

East Asian (EAS)

AF:

0.317

AC:

10814

AN:

34098

South Asian (SAS)

AF:

0.332

AC:

18790

AN:

56512

European-Finnish (FIN)

AF:

0.404

AC:

15602

AN:

38628

Middle Eastern (MID)

AF:

0.338

AC:

1052

AN:

3110

European-Non Finnish (NFE)

AF:

0.424

AC:

215167

AN:

507418

Other (OTH)

AF:

0.405

AC:

14485

AN:

35736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8442

16884

25327

33769

42211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4202

8404

12606

16808

21010

<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:

62649

AN:

152048

Hom.:

13074

Cov.:

AF XY:

0.409

AC XY:

30363

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.376

AC:

15609

AN:

41466

American (AMR)

AF:

0.442

AC:

6749

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1778

AN:

3464

East Asian (EAS)

AF:

0.296

AC:

1535

AN:

5184

South Asian (SAS)

AF:

0.347

AC:

1674

AN:

4818

European-Finnish (FIN)

AF:

0.394

AC:

4150

AN:

10540

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.440

AC:

29894

AN:

67990

Other (OTH)

AF:

0.409

AC:

866

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1924

3847

5771

7694

9618

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:

0.427

Hom.:

7112

Bravo

AF:

0.410

Asia WGS

AF:

0.362

AC:

1259

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

(source)

DANN

Benign

0.71

PhyloP100

-0.57

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