1-200111336-CAAAAAAA-CAAAAA

Variant names:

• chr1-200111336-CAA-C
• rs76894039
• NM_205860.3:c.1230+29_1230+30delAA

Variant summary

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

The NM_205860.3(NR5A2):​c.1230+29_1230+30delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,359,548 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.00024 (0 hom., cov: 27)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987
• 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 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+29_1230+30delAA		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1092+29_1092+30delAA		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1014+29_1014+30delAA		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+17delAA		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.1092+16_1092+17delAA		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000892175.1		c.1155+16_1155+17delAA		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 30 AN: 126402 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000861

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000783

Gnomad ASJ AF: 0.000320

Gnomad EAS AF: 0.000253

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00196

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000172

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0402 AC: 4109 AN: 102246 AF XY: 0.0425

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.0440

Gnomad ASJ exome AF: 0.0517

Gnomad EAS exome AF: 0.0403

Gnomad FIN exome AF: 0.0348

Gnomad NFE exome AF: 0.0368

Gnomad OTH exome AF: 0.0356

GnomAD4 exome AF: 0.0144 AC: 17720 AN: 1233146 Hom.: 0 AF XY: 0.0156 AC XY: 9500 AN XY: 609744

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

African (AFR) AF: 0.0118 AC: 306 AN: 25840

American (AMR) AF: 0.0327 AC: 808 AN: 24680

Ashkenazi Jewish (ASJ) AF: 0.0221 AC: 430 AN: 19416

East Asian (EAS) AF: 0.0267 AC: 894 AN: 33534

South Asian (SAS) AF: 0.0346 AC: 2206 AN: 63728

European-Finnish (FIN) AF: 0.0259 AC: 918 AN: 35430

Middle Eastern (MID) AF: 0.0158 AC: 70 AN: 4422

European-Non Finnish (NFE) AF: 0.0115 AC: 11217 AN: 975256

Other (OTH) AF: 0.0171 AC: 871 AN: 50840

⚠️ 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 AF: 0.000237 AC: 30 AN: 126402 Hom.: 0 Cov.: 27 AF XY: 0.000264 AC XY: 16 AN XY: 60702

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

African (AFR) AF: 0.0000861 AC: 3 AN: 34834

American (AMR) AF: 0.0000783 AC: 1 AN: 12776

Ashkenazi Jewish (ASJ) AF: 0.000320 AC: 1 AN: 3122

East Asian (EAS) AF: 0.000253 AC: 1 AN: 3950

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

European-Finnish (FIN) AF: 0.00196 AC: 14 AN: 7160

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

European-Non Finnish (NFE) AF: 0.000172 AC: 10 AN: 58162

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs76894039; hg19: chr1-200080464;