Genetic Variant NR5A2:c.1230+30dupA (chr1-200111336-C-CA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_205860.3(NR5A2):c.1230+30dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,390,840 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 27)

Exomes 𝑓: 0.013 ( 0 hom. )

Consequence

NR5A2
NM_205860.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.881

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 608 AD gene.

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.1230+30dupA	intron	N/A	NP_995582.1	O00482-1
NR5A2	NM_003822.5		c.1092+30dupA	intron	N/A	NP_003813.1	F1D8R9
NR5A2	NM_001276464.2		c.1014+30dupA	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.1230+15_1230+16insA	intron	N/A	ENSP00000356331.3	O00482-1
NR5A2	ENST00000236914.7	TSL:1	c.1092+15_1092+16insA	intron	N/A	ENSP00000236914.3	O00482-2
NR5A2	ENST00000892175.1		c.1155+15_1155+16insA	intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes

AF:

0.00480

AC:

607

AN:

126406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00172

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00380

Gnomad SAS

AF:

0.00214

Gnomad FIN

AF:

0.000417

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000602

Gnomad OTH

AF:

0.00579

GnomAD4 exome

AF:

0.0127

AC:

16055

AN:

1264420

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

8046

AN XY:

626032

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0162

AC:

426

AN:

26220

American (AMR)

AF:

0.0133

AC:

341

AN:

25682

Ashkenazi Jewish (ASJ)

AF:

0.00947

AC:

189

AN:

19964

East Asian (EAS)

AF:

0.0169

AC:

590

AN:

34838

South Asian (SAS)

AF:

0.0191

AC:

1278

AN:

66780

European-Finnish (FIN)

AF:

0.0118

AC:

433

AN:

36738

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

4568

European-Non Finnish (NFE)

AF:

0.0121

AC:

12073

AN:

997382

Other (OTH)

AF:

0.0130

AC:

679

AN:

52248

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.277

Heterozygous variant carriers

1587

3174

4762

6349

7936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

496

992

1488

1984

2480

<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:

0.00481

AC:

608

AN:

126420

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

281

AN XY:

60744

show subpopulations

African (AFR)

AF:

0.0148

AC:

516

AN:

34892

American (AMR)

AF:

0.00172

AC:

AN:

12798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3118

East Asian (EAS)

AF:

0.00355

AC:

AN:

3940

South Asian (SAS)

AF:

0.00215

AC:

AN:

3720

European-Finnish (FIN)

AF:

0.000417

AC:

AN:

7188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000602

AC:

AN:

58136

Other (OTH)

AF:

0.00579

AC:

AN:

1726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-200111336-CAAAAAAA-CAAAAAAAA

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