1-200111336-CAAAAAAA-CAAAAAAAA

Variant names:

• chr1-200111336-C-CA
• rs76894039
• NM_205860.3:c.1230+30dupA

Variant summary

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

The NM_205860.3(NR5A2):​c.1230+30dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,390,840 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 27)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

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 = 0.0127 (16055/1264420) while in subpopulation SAS AF= 0.0191 (1278/66780). AF 95% confidence interval is 0.0183. There are 0 homozygotes in gnomad4_exome. There are 8046 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 608 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1230+30dupA		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+15_1230+16insA		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1092+15_1092+16insA		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1014+15_1014+16insA		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 607 AN: 126406 Hom.: 4 Cov.: 27

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00380

Gnomad SAS AF: 0.00214

Gnomad FIN AF: 0.000417

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000602

Gnomad OTH AF: 0.00579

GnomAD4 exome AF: 0.0127 AC: 16055 AN: 1264420 Hom.: 0 Cov.: 0 AF XY: 0.0129 AC XY: 8046 AN XY: 626032

Gnomad4 AFR exome AF: 0.0162

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.00947

Gnomad4 EAS exome AF: 0.0169

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0130

GnomAD4 genome AF: 0.00481 AC: 608 AN: 126420 Hom.: 4 Cov.: 27 AF XY: 0.00463 AC XY: 281 AN XY: 60744

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00172

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00355

Gnomad4 SAS AF: 0.00215

Gnomad4 FIN AF: 0.000417

Gnomad4 NFE AF: 0.000602

Gnomad4 OTH AF: 0.00579

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;