1-200111336-CAAAAAAA-CAA

Variant names:

• chr1-200111336-CAAAAA-C
• rs76894039
• NM_205860.3:c.1230+26_1230+30delAAAAA

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+30delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,281,148 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: not found (cov: 27)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987
• Publications: 0 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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.1230+26_1230+30delAAAAA		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1092+26_1092+30delAAAAA		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1014+26_1014+30delAAAAA		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+16_1230+20delAAAAA		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.1092+16_1092+20delAAAAA		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000892175.1		c.1155+16_1155+20delAAAAA		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.0000187 AC: 24 AN: 1281148 Hom.: 0 AF XY: 0.0000237 AC XY: 15 AN XY: 634036

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

African (AFR) AF: 0.00 AC: 0 AN: 26434

American (AMR) AF: 0.0000387 AC: 1 AN: 25870

Ashkenazi Jewish (ASJ) AF: 0.0000994 AC: 2 AN: 20118

East Asian (EAS) AF: 0.0000284 AC: 1 AN: 35210

South Asian (SAS) AF: 0.0000738 AC: 5 AN: 67712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36956

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

European-Non Finnish (NFE) AF: 0.0000148 AC: 15 AN: 1011356

Other (OTH) AF: 0.00 AC: 0 AN: 52864

⚠️ 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.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99

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;