Genetic Variant NR5A2:c.1230+25_1230+30dupAAAAAA (chr1-200111336-C-CAAAAAA) – 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+25_1230+30dupAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000511 in 1,407,808 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000047 ( 1 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:

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ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 12 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
NR5A2	NM_205860.3	MANE Select	c.1230+25_1230+30dupAAAAAA	intron	N/A	NP_995582.1
NR5A2	NM_003822.5		c.1092+25_1092+30dupAAAAAA	intron	N/A	NP_003813.1
NR5A2	NM_001276464.2		c.1014+25_1014+30dupAAAAAA	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+16insAAAAAA	intron	N/A	ENSP00000356331.3
NR5A2	ENST00000236914.7	TSL:1	c.1092+15_1092+16insAAAAAA	intron	N/A	ENSP00000236914.3
NR5A2	ENST00000892175.1		c.1155+15_1155+16insAAAAAA	intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes

AF:

0.0000949

AC:

AN:

126474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000782

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000172

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000468

AC:

AN:

1281334

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

634156

show subpopulations

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

African (AFR)

AF:

0.00159

AC:

AN:

26412

American (AMR)

AF:

0.000193

AC:

AN:

25874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20124

East Asian (EAS)

AF:

0.00

AC:

AN:

35216

South Asian (SAS)

AF:

0.0000148

AC:

AN:

67742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4628

European-Non Finnish (NFE)

AF:

0.00000494

AC:

AN:

1011482

Other (OTH)

AF:

0.000132

AC:

AN:

52880

⚠️ 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: 0.343

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000949

AC:

AN:

126474

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

60744

show subpopulations

African (AFR)

AF:

0.000287

AC:

AN:

34836

American (AMR)

AF:

0.0000782

AC:

AN:

12788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3122

East Asian (EAS)

AF:

0.00

AC:

AN:

3952

South Asian (SAS)

AF:

0.00

AC:

AN:

3744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0000172

AC:

AN:

58190

Other (OTH)

AF:

0.00

AC:

AN:

1728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

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

Splicing

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

Publications

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1-200111336-CAAAAAAA-CAAAAAAAAAAAAA

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