rs2816949

Variant names:

• chr1-200028650-A-G
• rs2816949
• NM_205860.3:c.64+739A>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.64+739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,092 control chromosomes in the GnomAD database, including 13,670 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 0.35 (13670 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.64+739A>G		intron	N/A	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.64+739A>G		intron	N/A	NP_003813.1	F1D8R9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.64+739A>G		intron	N/A	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.64+739A>G		intron	N/A	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000447034.1	TSL:1	c.28+739A>G		intron	N/A	ENSP00000414888.1	H0Y7S7

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52481 AN: 151972 Hom.: 13619 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.346 AC: 52584 AN: 152092 Hom.: 13670 Cov.: 32 AF XY: 0.335 AC XY: 24903 AN XY: 74380

African (AFR) AF: 0.737 AC: 30548 AN: 41456

American (AMR) AF: 0.233 AC: 3554 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 769 AN: 3472

East Asian (EAS) AF: 0.0675 AC: 349 AN: 5170

South Asian (SAS) AF: 0.0899 AC: 434 AN: 4828

European-Finnish (FIN) AF: 0.158 AC: 1679 AN: 10594

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

European-Non Finnish (NFE) AF: 0.211 AC: 14343 AN: 67976

Other (OTH) AF: 0.316 AC: 668 AN: 2116

Alfa AF: 0.270 Hom.: 18256

Bravo AF: 0.370

Asia WGS AF: 0.143 AC: 502 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	3.6
DANN	Benign	0.54
PhyloP100		0.085
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: rs2816949; hg19: chr1-199997778; COSMIC: COSV52655530;