rs76894039

Positions:

• chr1-200111336-CAAAA-C
• chr1-200111336-CAAAA-CA
• chr1-200111336-CAAAA-CAA
• chr1-200111336-CAAAA-CAAA
• chr1-200111336-CAAAA-CAAAAA
• chr1-200111336-CAAAA-CAAAAAA
• chr1-200111336-CAAAA-CAAAAAAA
• chr1-200111336-CAAAA-CAAAAAAAA
• chr1-200111336-CAAAA-CAAAAAAAAA
• chr1-200111336-CAAAA-CAAAAAAAAAA
• chr1-200111336-CAAAA-CAAAAAAAAAAA
• chr1-200111336-CAAAA-CAAAAAAAAAAAAA
• chr1-200111336-CAAAA-CAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_205860.3(NR5A2):​c.1230+27_1230+30del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,405,902 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.00023 (1 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 289 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1230+27_1230+30del		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+27_1230+30del		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.1092+27_1092+30del		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.1014+27_1014+30del		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.00000791 AC: 1 AN: 126480 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

GnomAD4 exome AF: 0.000226 AC: 289 AN: 1279422 Hom.: 1 AF XY: 0.000273 AC XY: 173 AN XY: 633100

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.000776

Gnomad4 ASJ exome AF: 0.000597

Gnomad4 EAS exome AF: 0.000285

Gnomad4 SAS exome AF: 0.000786

Gnomad4 FIN exome AF: 0.000733

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.000227

GnomAD4 genome AF: 0.00000791 AC: 1 AN: 126480 Hom.: 0 Cov.: 27 AF XY: 0.0000165 AC XY: 1 AN XY: 60752

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000172

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

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;