rs3762399

Variant names:

• chr1-200032998-C-A
• rs3762399
• NM_205860.3:c.64+5087C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_205860.3(NR5A2):​c.64+5087C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,190 control chromosomes in the GnomAD database, including 1,727 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 0.12 (1727 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 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.64+5087C>A		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.64+5087C>A		intron	N/A	NP_003813.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.64+5087C>A		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.64+5087C>A		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000447034.1	TSL:1	c.28+5087C>A		intron	N/A	ENSP00000414888.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18897 AN: 152072 Hom.: 1714 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18931 AN: 152190 Hom.: 1727 Cov.: 32 AF XY: 0.120 AC XY: 8958 AN XY: 74414

African (AFR) AF: 0.257 AC: 10646 AN: 41484

American (AMR) AF: 0.0929 AC: 1421 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3468

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5182

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4830

European-Finnish (FIN) AF: 0.0592 AC: 628 AN: 10604

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5273 AN: 68016

Other (OTH) AF: 0.115 AC: 241 AN: 2104

Alfa AF: 0.0924 Hom.: 1442

Bravo AF: 0.135

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.65
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3762399; hg19: chr1-200002126;