1-200111336-CAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr1-200111336-C-CAAAA
• rs76894039
• NM_205860.3:c.1230+27_1230+30dupAAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_205860.3(NR5A2):​c.1230+27_1230+30dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,407,414 control chromosomes in the GnomAD database, including 34 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0069 (20 hom., cov: 27)
  • Exomes 𝑓: 0.00062 (14 hom.)
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00689 (871/126470) while in subpopulation AFR AF = 0.0237 (828/34888). AF 95% confidence interval is 0.0224. There are 20 homozygotes in GnomAd4. There are 415 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAd4 at 871 AD gene.

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+27_1230+30dupAAAA		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1092+27_1092+30dupAAAA		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1014+27_1014+30dupAAAA		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+16insAAAA		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.1092+15_1092+16insAAAA		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000892175.1		c.1155+15_1155+16insAAAA		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 876 AN: 126454 Hom.: 22 Cov.: 27

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000267

Gnomad FIN AF: 0.000139

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000172

Gnomad OTH AF: 0.00405

GnomAD4 exome AF: 0.000617 AC: 790 AN: 1280944 Hom.: 14 Cov.: 0 AF XY: 0.000568 AC XY: 360 AN XY: 633956

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

African (AFR) AF: 0.0212 AC: 556 AN: 26214

American (AMR) AF: 0.000696 AC: 18 AN: 25862

Ashkenazi Jewish (ASJ) AF: 0.000994 AC: 20 AN: 20116

East Asian (EAS) AF: 0.000114 AC: 4 AN: 35214

South Asian (SAS) AF: 0.000133 AC: 9 AN: 67738

European-Finnish (FIN) AF: 0.0000541 AC: 2 AN: 36964

Middle Eastern (MID) AF: 0.000216 AC: 1 AN: 4628

European-Non Finnish (NFE) AF: 0.000111 AC: 112 AN: 1011368

Other (OTH) AF: 0.00129 AC: 68 AN: 52840

⚠️ 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: 0.00689 AC: 871 AN: 126470 Hom.: 20 Cov.: 27 AF XY: 0.00683 AC XY: 415 AN XY: 60772

African (AFR) AF: 0.0237 AC: 828 AN: 34888

American (AMR) AF: 0.00258 AC: 33 AN: 12800

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3942

South Asian (SAS) AF: 0.000269 AC: 1 AN: 3724

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000172 AC: 1 AN: 58176

Other (OTH) AF: 0.00405 AC: 7 AN: 1728

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism

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;