1-200111336-CAAAAAAA-CAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

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. 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

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0144 (17720/1233146) while in subpopulation SAS AF= 0.0346 (2206/63728). AF 95% confidence interval is 0.0334. There are 0 homozygotes in gnomad4_exome. There are 9500 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1230+29_1230+30delAA		intron_variant	Intron 6 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+16_1230+17delAA		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1092+16_1092+17delAA		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1014+16_1014+17delAA		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

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

GnomAD3 exomes AF: 0.0402 AC: 4109 AN: 102246 Hom.: 2 AF XY: 0.0425 AC XY: 2337 AN XY: 54958

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 SAS exome AF: 0.0642

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

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0327

Gnomad4 ASJ exome AF: 0.0221

Gnomad4 EAS exome AF: 0.0267

Gnomad4 SAS exome AF: 0.0346

Gnomad4 FIN exome AF: 0.0259

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.0171

GnomAD4 genome AF: 0.000237 AC: 30 AN: 126402 Hom.: 0 Cov.: 27 AF XY: 0.000264 AC XY: 16 AN XY: 60702

Gnomad4 AFR AF: 0.0000861

Gnomad4 AMR AF: 0.0000783

Gnomad4 ASJ AF: 0.000320

Gnomad4 EAS AF: 0.000253

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00196

Gnomad4 NFE AF: 0.000172

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs76894039; hg19: chr1-200080464;