Genetic Variant NR5A2:c.1230+26_1230+30dupAAAAA (chr1-200111336-C-CAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_205860.3(NR5A2):c.1230+26_1230+30dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 107 hom., cov: 27)

Exomes 𝑓: 0.00056 ( 13 hom. )

Failed GnomAD Quality Control

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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
NR5A2	NM_205860.3	MANE Select	c.1230+26_1230+30dupAAAAA	intron	N/A	NP_995582.1
NR5A2	NM_003822.5		c.1092+26_1092+30dupAAAAA	intron	N/A	NP_003813.1
NR5A2	NM_001276464.2		c.1014+26_1014+30dupAAAAA	intron	N/A	NP_001263393.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.1230+15_1230+16insAAAAA	intron	N/A	ENSP00000356331.3
NR5A2	ENST00000236914.7	TSL:1	c.1092+15_1092+16insAAAAA	intron	N/A	ENSP00000236914.3
NR5A2	ENST00000892175.1		c.1155+15_1155+16insAAAAA	intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2387

AN:

126372

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00649

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.000139

Gnomad MID

AF:

0.0154

Gnomad NFE

AF:

0.000137

Gnomad OTH

AF:

0.0150

GnomAD4 exome

AF:

0.000560

AC:

717

AN:

1281054

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

308

AN XY:

634026

show subpopulations

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

African (AFR)

AF:

0.0225

AC:

591

AN:

26210

American (AMR)

AF:

0.000541

AC:

AN:

25866

Ashkenazi Jewish (ASJ)

AF:

0.0000497

AC:

AN:

20124

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35216

South Asian (SAS)

AF:

0.00

AC:

AN:

67736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36976

Middle Eastern (MID)

AF:

0.000648

AC:

AN:

4628

European-Non Finnish (NFE)

AF:

0.0000465

AC:

AN:

1011454

Other (OTH)

AF:

0.00114

AC:

AN:

52844

⚠️ 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: 0.345

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0189

AC:

2387

AN:

126388

Hom.:

107

Cov.:

AF XY:

0.0181

AC XY:

1098

AN XY:

60732

show subpopulations

African (AFR)

AF:

0.0650

AC:

2262

AN:

34804

American (AMR)

AF:

0.00649

AC:

AN:

12798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3122

East Asian (EAS)

AF:

0.00

AC:

AN:

3942

South Asian (SAS)

AF:

0.000806

AC:

AN:

3724

European-Finnish (FIN)

AF:

0.000139

AC:

AN:

7188

Middle Eastern (MID)

AF:

0.0169

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000138

AC:

AN:

58180

Other (OTH)

AF:

0.0150

AC:

AN:

1728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-200111336-CAAAAAAA-CAAAAAAAAAAAA

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