Genetic Variant NR5A2:c.1378+37G>A (chr1-200120992-G-A) – 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+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,608,088 control chromosomes in the GnomAD database, including 63,449 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 0.26 ( 5472 hom., cov: 33)

Exomes 𝑓: 0.28 ( 57977 hom. )

Consequence

NR5A2
NM_205860.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.954

Publications

10 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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 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.1378+37G>A	intron	N/A	NP_995582.1	O00482-1
NR5A2	NM_003822.5		c.1240+37G>A	intron	N/A	NP_003813.1	F1D8R9
NR5A2	NM_001276464.2		c.1162+37G>A	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.1378+37G>A	intron	N/A	ENSP00000356331.3	O00482-1
NR5A2	ENST00000236914.7	TSL:1	c.1240+37G>A	intron	N/A	ENSP00000236914.3	O00482-2
NR5A2	ENST00000892175.1		c.1303+37G>A	intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39693

AN:

151996

Hom.:

5457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.277

AC:

69146

AN:

249570

AF XY:

0.276

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.280

AC:

407394

AN:

1455974

Hom.:

57977

Cov.:

AF XY:

0.280

AC XY:

202783

AN XY:

724564

show subpopulations

African (AFR)

AF:

0.178

AC:

5926

AN:

33286

American (AMR)

AF:

0.339

AC:

15042

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

8388

AN:

26024

East Asian (EAS)

AF:

0.229

AC:

9073

AN:

39572

South Asian (SAS)

AF:

0.257

AC:

22013

AN:

85688

European-Finnish (FIN)

AF:

0.270

AC:

14342

AN:

53200

Middle Eastern (MID)

AF:

0.225

AC:

1297

AN:

5754

European-Non Finnish (NFE)

AF:

0.284

AC:

314960

AN:

1107834

Other (OTH)

AF:

0.272

AC:

16353

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

13247

26495

39742

52990

66237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10354

20708

31062

41416

51770

<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:

0.261

AC:

39727

AN:

152114

Hom.:

5472

Cov.:

AF XY:

0.261

AC XY:

19419

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.188

AC:

7787

AN:

41500

American (AMR)

AF:

0.334

AC:

5101

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1137

AN:

3470

East Asian (EAS)

AF:

0.223

AC:

1154

AN:

5176

South Asian (SAS)

AF:

0.265

AC:

1276

AN:

4824

European-Finnish (FIN)

AF:

0.257

AC:

2715

AN:

10562

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.288

AC:

19612

AN:

67988

Other (OTH)

AF:

0.297

AC:

627

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1491

2982

4473

5964

7455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.281

Hom.:

26452

Bravo

AF:

0.262

Asia WGS

AF:

0.281

AC:

979

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.39

(source)

DANN

Benign

0.49

PhyloP100

-0.95

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