1-200085949-G-T

Variant names:

• chr1-200085949-G-T
• rs2816928
• NM_205860.3:c.1111-25253G>T

Variant summary

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

The NM_205860.3(NR5A2):​c.1111-25253G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,898 control chromosomes in the GnomAD database, including 21,104 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 0.53 (21104 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.1111-25253G>T		intron	N/A	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.973-25253G>T		intron	N/A	NP_003813.1	F1D8R9
	NR5A2	NM_001276464.2		c.895-25253G>T		intron	N/A	NP_001263393.1	O00482-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.1111-25253G>T		intron	N/A	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.973-25253G>T		intron	N/A	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000892175.1		c.1036-25253G>T		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79778 AN: 151780 Hom.: 21084 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.526 AC: 79838 AN: 151898 Hom.: 21104 Cov.: 32 AF XY: 0.528 AC XY: 39172 AN XY: 74228

African (AFR) AF: 0.584 AC: 24162 AN: 41406

American (AMR) AF: 0.525 AC: 8021 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1923 AN: 3466

East Asian (EAS) AF: 0.519 AC: 2678 AN: 5162

South Asian (SAS) AF: 0.543 AC: 2618 AN: 4820

European-Finnish (FIN) AF: 0.523 AC: 5512 AN: 10548

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33265 AN: 67918

Other (OTH) AF: 0.521 AC: 1098 AN: 2108

Alfa AF: 0.500 Hom.: 2573

Bravo AF: 0.529

Asia WGS AF: 0.522 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.93
DANN	Benign	0.31
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: rs2816928; hg19: chr1-200055077;