1-200170222-C-T

Variant names:

• chr1-200170222-C-T
• rs2246923
• NM_205860.3:c.1379-3741C>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.1379-3741C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,938 control chromosomes in the GnomAD database, including 8,763 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 0.33 (8763 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 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.1379-3741C>T		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1241-3741C>T		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1163-3741C>T		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.1379-3741C>T		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.1241-3741C>T		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000544748.5	TSL:2	c.1163-3741C>T		intron	N/A	ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50762 AN: 151820 Hom.: 8752 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.334 AC: 50809 AN: 151938 Hom.: 8763 Cov.: 32 AF XY: 0.336 AC XY: 24962 AN XY: 74240

African (AFR) AF: 0.403 AC: 16700 AN: 41444

American (AMR) AF: 0.316 AC: 4820 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3468

East Asian (EAS) AF: 0.427 AC: 2206 AN: 5172

South Asian (SAS) AF: 0.330 AC: 1588 AN: 4810

European-Finnish (FIN) AF: 0.340 AC: 3576 AN: 10526

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20169 AN: 67954

Other (OTH) AF: 0.318 AC: 669 AN: 2104

Alfa AF: 0.306 Hom.: 21839

Bravo AF: 0.335

Asia WGS AF: 0.363 AC: 1262 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		0.23
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: rs2246923; hg19: chr1-200139350;