Genetic Variant NM_205860.3:c.1230+24_1230+30dupAAAAAAA (chr1-200111336-C-CAAAAAAA) – 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+24_1230+30dupAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 1,407,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000079 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000055 ( 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:

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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+24_1230+30dupAAAAAAA	intron	N/A	NP_995582.1
NR5A2	NM_003822.5		c.1092+24_1092+30dupAAAAAAA	intron	N/A	NP_003813.1
NR5A2	NM_001276464.2		c.1014+24_1014+30dupAAAAAAA	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+16insAAAAAAA	intron	N/A	ENSP00000356331.3
NR5A2	ENST00000236914.7	TSL:1	c.1092+15_1092+16insAAAAAAA	intron	N/A	ENSP00000236914.3
NR5A2	ENST00000892175.1		c.1155+15_1155+16insAAAAAAA	intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes

AF:

0.00000791

AC:

AN:

126482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000546

AC:

AN:

1281358

Hom.:

Cov.:

AF XY:

0.00000473

AC XY:

AN XY:

634170

show subpopulations

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

African (AFR)

AF:

0.000265

AC:

AN:

26436

American (AMR)

AF:

0.00

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:

0.00

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:

0.00

AC:

AN:

1011484

Other (OTH)

AF:

0.00

AC:

AN:

52878

⚠️ 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: 0.282

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000791

AC:

AN:

126482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60752

show subpopulations

African (AFR)

AF:

0.0000287

AC:

AN:

34844

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

58190

Other (OTH)

AF:

0.00

AC:

AN:

1728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over