chr1-200059303-C-T

Variant names:

• chr1-200059303-C-T
• rs10919803
• NM_205860.3:c.1110+10485C>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.1110+10485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,066 control chromosomes in the GnomAD database, including 1,381 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 0.13 (1381 hom., cov: 31)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 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.1110+10485C>T		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.972+10485C>T		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.894+10485C>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.1110+10485C>T		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.972+10485C>T		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000544748.5	TSL:2	c.894+10485C>T		intron	N/A	ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19474 AN: 151948 Hom.: 1375 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.128 AC: 19485 AN: 152066 Hom.: 1381 Cov.: 31 AF XY: 0.128 AC XY: 9534 AN XY: 74334

African (AFR) AF: 0.184 AC: 7644 AN: 41446

American (AMR) AF: 0.105 AC: 1601 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5178

South Asian (SAS) AF: 0.0962 AC: 463 AN: 4812

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10592

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7602 AN: 67980

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.117 Hom.: 842

Bravo AF: 0.130

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.64
PhyloP100		0.023
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: rs10919803; hg19: chr1-200028431;