chr1-200047018-T-C

Variant names:

• chr1-200047018-T-C
• rs2821367
• NM_205860.3:c.464-1154T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_205860.3(NR5A2):​c.464-1154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,004 control chromosomes in the GnomAD database, including 16,950 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 0.43 (16950 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 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.464-1154T>C		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.326-1154T>C		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.248-1154T>C		intron	N/A	NP_001263393.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.464-1154T>C		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.326-1154T>C		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000367357.3	TSL:1	c.224-1154T>C		intron	N/A	ENSP00000356326.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65003 AN: 151886 Hom.: 16905 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.428 AC: 65089 AN: 152004 Hom.: 16950 Cov.: 32 AF XY: 0.420 AC XY: 31187 AN XY: 74302

African (AFR) AF: 0.733 AC: 30376 AN: 41430

American (AMR) AF: 0.320 AC: 4894 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3466

East Asian (EAS) AF: 0.0734 AC: 381 AN: 5188

South Asian (SAS) AF: 0.213 AC: 1029 AN: 4826

European-Finnish (FIN) AF: 0.303 AC: 3193 AN: 10544

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22474 AN: 67966

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.357 Hom.: 8003

Bravo AF: 0.444

Asia WGS AF: 0.187 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.17
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: rs2821367; hg19: chr1-200016146; COSMIC: COSV52647046; COSMIC: COSV52647046;