1-200038304-A-G

Variant names:

• chr1-200038304-A-G
• rs3790844
• NM_205860.3:c.65-1354A>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.65-1354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,158 control chromosomes in the GnomAD database, including 5,952 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 0.25 (5952 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 84 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 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.65-1354A>G		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.65-5470A>G		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.65-1354A>G		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.65-5470A>G		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000447034.1	TSL:1	c.29-397A>G		intron	N/A	ENSP00000414888.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38015 AN: 152040 Hom.: 5948 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.250 AC: 38017 AN: 152158 Hom.: 5952 Cov.: 32 AF XY: 0.264 AC XY: 19653 AN XY: 74406

African (AFR) AF: 0.127 AC: 5286 AN: 41550

American (AMR) AF: 0.339 AC: 5178 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3442 AN: 5164

South Asian (SAS) AF: 0.438 AC: 2114 AN: 4824

European-Finnish (FIN) AF: 0.401 AC: 4243 AN: 10592

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16086 AN: 67964

Other (OTH) AF: 0.243 AC: 514 AN: 2112

Alfa AF: 0.243 Hom.: 23990

Bravo AF: 0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.86
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: rs3790844; hg19: chr1-200007432; COSMIC: COSV52645441;