1-200111336-CAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chr1-200111336-C-CAAAAAAAAA
• rs76894039
• NM_205860.3:c.1230+22_1230+30dupAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_205860.3(NR5A2):​c.1230+22_1230+30dupAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 126,482 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.1230+22_1230+30dupAAAAAAAAA		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1092+22_1092+30dupAAAAAAAAA		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1014+22_1014+30dupAAAAAAAAA		intron	N/A	NP_001263393.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0000158 AC: 2 AN: 126482 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

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: 0.000139

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000172

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1281362 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 634170

African (AFR) AF: 0.00 AC: 0 AN: 26438

American (AMR) AF: 0.00 AC: 0 AN: 25874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20124

East Asian (EAS) AF: 0.00 AC: 0 AN: 35216

South Asian (SAS) AF: 0.00 AC: 0 AN: 67742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1011484

Other (OTH) AF: 0.00 AC: 0 AN: 52880

GnomAD4 genome AF: 0.0000158 AC: 2 AN: 126482 Hom.: 0 Cov.: 27 AF XY: 0.0000329 AC XY: 2 AN XY: 60752

African (AFR) AF: 0.00 AC: 0 AN: 34844

American (AMR) AF: 0.00 AC: 0 AN: 12788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3122

East Asian (EAS) AF: 0.00 AC: 0 AN: 3952

South Asian (SAS) AF: 0.00 AC: 0 AN: 3744

European-Finnish (FIN) AF: 0.000139 AC: 1 AN: 7188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000172 AC: 1 AN: 58190

Other (OTH) AF: 0.00 AC: 0 AN: 1728

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

Other links and lift over

dbSNP: rs76894039; hg19: chr1-200080464;