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. Variant got -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

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 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 male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 871 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1230+27_1230+30dupAAAA		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+16insAAAA		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1092+15_1092+16insAAAA		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1014+15_1014+16insAAAA		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

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

Gnomad4 AFR exome AF: 0.0212

Gnomad4 AMR exome AF: 0.000696

Gnomad4 ASJ exome AF: 0.000994

Gnomad4 EAS exome AF: 0.000114

Gnomad4 SAS exome AF: 0.000133

Gnomad4 FIN exome AF: 0.0000541

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00689 AC: 871 AN: 126470 Hom.: 20 Cov.: 27 AF XY: 0.00683 AC XY: 415 AN XY: 60772

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.00258

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000269

Gnomad4 FIN AF: 0.000139

Gnomad4 NFE AF: 0.0000172

Gnomad4 OTH AF: 0.00405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;