1-200045432-C-G

Variant names:

• chr1-200045432-C-G
• rs41300849
• NM_205860.3:c.322-11C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_205860.3(NR5A2):​c.322-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Scores: Splicing: ADA: 0.1013
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).

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.322-11C>G		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.184-11C>G		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.106-11C>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.322-11C>G		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.184-11C>G		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000367357.3	TSL:1	c.82-11C>G		intron	N/A	ENSP00000356326.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412554 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 702024

African (AFR) AF: 0.00 AC: 0 AN: 30482

American (AMR) AF: 0.00 AC: 0 AN: 33404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24054

East Asian (EAS) AF: 0.00 AC: 0 AN: 38350

South Asian (SAS) AF: 0.00 AC: 0 AN: 78212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091934

Other (OTH) AF: 0.00 AC: 0 AN: 58168

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.10
dbscSNV1_RF	Benign	0.35
SpliceAI score (max)		0.060		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: rs41300849; hg19: chr1-200014560;