1-200111336-CAAAAAAA-CAAAA

Variant names:

• chr1-200111336-CAAA-C
• rs76894039
• NM_205860.3:c.1230+28_1230+30delAAA

Variant summary

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

The NM_205860.3(NR5A2):​c.1230+28_1230+30delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,396,206 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: 0.0019 (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+28_1230+30delAAA		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1092+28_1092+30delAAA		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1014+28_1014+30delAAA		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+18delAAA		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.1092+16_1092+18delAAA		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000892175.1		c.1155+16_1155+18delAAA		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.00000791 AC: 1 AN: 126462 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000172

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0102 AC: 1046 AN: 102246 AF XY: 0.0110

Gnomad AFR exome AF: 0.00590

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.0226

Gnomad EAS exome AF: 0.00882

Gnomad FIN exome AF: 0.00943

Gnomad NFE exome AF: 0.00852

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.00192 AC: 2441 AN: 1269744 Hom.: 0 AF XY: 0.00219 AC XY: 1373 AN XY: 628070

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

African (AFR) AF: 0.00145 AC: 38 AN: 26264

American (AMR) AF: 0.00663 AC: 169 AN: 25486

Ashkenazi Jewish (ASJ) AF: 0.00483 AC: 96 AN: 19858

East Asian (EAS) AF: 0.00288 AC: 100 AN: 34780

South Asian (SAS) AF: 0.00573 AC: 380 AN: 66284

European-Finnish (FIN) AF: 0.00472 AC: 172 AN: 36406

Middle Eastern (MID) AF: 0.000870 AC: 4 AN: 4596

European-Non Finnish (NFE) AF: 0.00135 AC: 1357 AN: 1003744

Other (OTH) AF: 0.00239 AC: 125 AN: 52326

⚠️ 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: 0.00000791 AC: 1 AN: 126462 Hom.: 0 Cov.: 27 AF XY: 0.0000165 AC XY: 1 AN XY: 60738

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

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: 0.00 AC: 0 AN: 7176

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

European-Non Finnish (NFE) AF: 0.0000172 AC: 1 AN: 58182

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.

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;