rs2816948

Variant names:

• chr1-200027557-C-G
• rs2816948
• NM_205860.3:c.-291C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_205860.3(NR5A2):​c.-291C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 289,094 control chromosomes in the GnomAD database, including 3,669 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2571 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1098 hom.)
• Consequence: NR5A2 NM_205860.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.-291C>G		upstream_gene_variant		ENST00000367362.8	NP_995582.1
NR5A2	NM_003822.5	c.-291C>G		upstream_gene_variant			NP_003813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.-291C>G		upstream_gene_variant		1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.-291C>G		upstream_gene_variant		1		ENSP00000236914.3
NR5A2	ENST00000474307.1	n.-291C>G		upstream_gene_variant		1		ENSP00000436776.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25199 AN: 152076 Hom.: 2563 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.116 AC: 15892 AN: 136900 Hom.: 1098 Cov.: 0 AF XY: 0.115 AC XY: 7946 AN XY: 69360

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.0281

Gnomad4 SAS exome AF: 0.0582

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.166 AC: 25234 AN: 152194 Hom.: 2571 Cov.: 32 AF XY: 0.161 AC XY: 11944 AN XY: 74404

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0291

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.162

Alfa AF: 0.156 Hom.: 284

Bravo AF: 0.172

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2816948; hg19: chr1-199996685;