rs2816948

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205860.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.-291C>G		upstream_gene	N/A	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.-291C>G		upstream_gene	N/A	NP_003813.1	F1D8R9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.-291C>G		upstream_gene	N/A	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.-291C>G		upstream_gene	N/A	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000474307.1	TSL:1	n.-291C>G		upstream_gene	N/A	ENSP00000436776.1	E9PQH2

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

African (AFR) AF: 0.294 AC: 1284 AN: 4364

American (AMR) AF: 0.105 AC: 395 AN: 3748

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 563 AN: 5288

East Asian (EAS) AF: 0.0281 AC: 281 AN: 9998

South Asian (SAS) AF: 0.0582 AC: 337 AN: 5794

European-Finnish (FIN) AF: 0.101 AC: 833 AN: 8276

Middle Eastern (MID) AF: 0.0808 AC: 53 AN: 656

European-Non Finnish (NFE) AF: 0.123 AC: 10983 AN: 89332

Other (OTH) AF: 0.123 AC: 1163 AN: 9444

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

African (AFR) AF: 0.293 AC: 12154 AN: 41496

American (AMR) AF: 0.112 AC: 1707 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3472

East Asian (EAS) AF: 0.0291 AC: 151 AN: 5190

South Asian (SAS) AF: 0.0693 AC: 334 AN: 4820

European-Finnish (FIN) AF: 0.0991 AC: 1050 AN: 10592

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8951 AN: 68014

Other (OTH) AF: 0.162 AC: 343 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.56
PromoterAI		-0.071	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2816948; hg19: chr1-199996685;