rs2821368

Variant names:

• chr1-200048458-C-G
• rs2821368
• NM_205860.3:c.750C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-200048458-C-G
• chr1-200048458-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_205860.3(NR5A2):​c.750C>G​(p.Pro250Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,613,982 control chromosomes in the GnomAD database, including 32,724 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6860 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25864 hom.)
• Consequence: NR5A2 NM_205860.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 13 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 -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-0.095 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.750C>G	p.Pro250Pro	synonymous	Exon 5 of 8	NP_995582.1
	NR5A2	NM_003822.5		c.612C>G	p.Pro204Pro	synonymous	Exon 4 of 7	NP_003813.1
	NR5A2	NM_001276464.2		c.534C>G	p.Pro178Pro	synonymous	Exon 4 of 7	NP_001263393.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.750C>G	p.Pro250Pro	synonymous	Exon 5 of 8	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.612C>G	p.Pro204Pro	synonymous	Exon 4 of 7	ENSP00000236914.3
	NR5A2	ENST00000367357.3	TSL:1	c.510C>G	p.Pro170Pro	synonymous	Exon 3 of 4	ENSP00000356326.3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39604 AN: 152000 Hom.: 6845 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.258

GnomAD2 exomes AF: 0.183 AC: 46071 AN: 251412 AF XY: 0.178

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.0370

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.176 AC: 257721 AN: 1461864 Hom.: 25864 Cov.: 36 AF XY: 0.175 AC XY: 127097 AN XY: 727232

African (AFR) AF: 0.521 AC: 17429 AN: 33480

American (AMR) AF: 0.140 AC: 6259 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7630 AN: 26136

East Asian (EAS) AF: 0.0282 AC: 1121 AN: 39700

South Asian (SAS) AF: 0.139 AC: 11974 AN: 86258

European-Finnish (FIN) AF: 0.195 AC: 10441 AN: 53408

Middle Eastern (MID) AF: 0.253 AC: 1462 AN: 5768

European-Non Finnish (NFE) AF: 0.171 AC: 189832 AN: 1111994

Other (OTH) AF: 0.192 AC: 11573 AN: 60396

GnomAD4 genome AF: 0.261 AC: 39657 AN: 152118 Hom.: 6860 Cov.: 32 AF XY: 0.258 AC XY: 19167 AN XY: 74356

African (AFR) AF: 0.492 AC: 20384 AN: 41468

American (AMR) AF: 0.199 AC: 3032 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3470

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5186

South Asian (SAS) AF: 0.126 AC: 608 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2081 AN: 10582

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.171 AC: 11614 AN: 68006

Other (OTH) AF: 0.254 AC: 535 AN: 2110

Alfa AF: 0.206 Hom.: 1227

Bravo AF: 0.274

Asia WGS AF: 0.105 AC: 365 AN: 3478

EpiCase AF: 0.183

EpiControl AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.0
DANN	Benign	0.70
PhyloP100		-0.095
Mutation Taster		=89/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2821368; hg19: chr1-200017586; COSMIC: COSV52646154; COSMIC: COSV52646154;