chr1-200093730-T-G

Variant names:

• chr1-200093730-T-G
• rs2737667
• NM_205860.3:c.1111-17472T>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.1111-17472T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,138 control chromosomes in the GnomAD database, including 8,112 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 0.31 (8112 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 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.1111-17472T>G		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.973-17472T>G		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.895-17472T>G		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.1111-17472T>G		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.973-17472T>G		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000544748.5	TSL:2	c.895-17472T>G		intron	N/A	ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47173 AN: 152020 Hom.: 8089 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.311 AC: 47240 AN: 152138 Hom.: 8112 Cov.: 32 AF XY: 0.318 AC XY: 23650 AN XY: 74392

African (AFR) AF: 0.394 AC: 16330 AN: 41490

American (AMR) AF: 0.369 AC: 5644 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3468

East Asian (EAS) AF: 0.538 AC: 2781 AN: 5170

South Asian (SAS) AF: 0.395 AC: 1899 AN: 4812

European-Finnish (FIN) AF: 0.295 AC: 3127 AN: 10610

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15986 AN: 67996

Other (OTH) AF: 0.296 AC: 623 AN: 2108

Alfa AF: 0.153 Hom.: 304

Bravo AF: 0.319

Asia WGS AF: 0.484 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.56
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: rs2737667; hg19: chr1-200062858;