chr1-200048458-C-G

Position:

• chr1-200048458-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong 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. 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 0.26 (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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.750C>G	p.Pro250Pro	synonymous_variant	5/8	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.750C>G	p.Pro250Pro	synonymous_variant	5/8	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.612C>G	p.Pro204Pro	synonymous_variant	4/7	1		ENSP00000236914.3
NR5A2	ENST00000367357.3	c.510C>G	p.Pro170Pro	synonymous_variant	3/4	1		ENSP00000356326.3
NR5A2	ENST00000544748.5	c.534C>G	p.Pro178Pro	synonymous_variant	4/7	2		ENSP00000439116.1

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

GnomAD3 exomes AF: 0.183 AC: 46071 AN: 251412 Hom.: 5460 AF XY: 0.178 AC XY: 24240 AN XY: 135880

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 SAS exome AF: 0.134

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

Gnomad4 AFR exome AF: 0.521

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.0282

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.192

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

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.254

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.0
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

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