1-200082146-G-A

Variant names:

• chr1-200082146-G-A
• rs2821313
• NM_205860.3:c.1111-29056G>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.1111-29056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,818 control chromosomes in the GnomAD database, including 17,581 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 0.48 (17581 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 4 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 (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1111-29056G>A		intron_variant	Intron 5 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1111-29056G>A		intron_variant	Intron 5 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.973-29056G>A		intron_variant	Intron 4 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.895-29056G>A		intron_variant	Intron 4 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72972 AN: 151700 Hom.: 17571 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.481 AC: 73011 AN: 151818 Hom.: 17581 Cov.: 32 AF XY: 0.483 AC XY: 35853 AN XY: 74184

African (AFR) AF: 0.490 AC: 20292 AN: 41398

American (AMR) AF: 0.495 AC: 7555 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2428 AN: 5140

South Asian (SAS) AF: 0.497 AC: 2391 AN: 4810

European-Finnish (FIN) AF: 0.496 AC: 5211 AN: 10514

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31694 AN: 67928

Other (OTH) AF: 0.486 AC: 1024 AN: 2106

Alfa AF: 0.475 Hom.: 27222

Bravo AF: 0.481

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8
DANN	Benign	0.59
PhyloP100		0.019
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: rs2821313; hg19: chr1-200051274;