rs2816949

Positions:

• chr1-200028650-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.64+739A>G		intron_variant		ENST00000367362.8
NR5A2	NM_003822.5	c.64+739A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.64+739A>G		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.64+739A>G		intron_variant		1		A1
NR5A2	ENST00000447034.1	c.29+739A>G		intron_variant		1
NR5A2	ENST00000474307.1	c.65-383A>G		intron_variant, NMD_transcript_variant		1

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

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0675

Gnomad4 SAS AF: 0.0899

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.316

Alfa AF: 0.230 Hom.: 6926

Bravo AF: 0.370

Asia WGS AF: 0.143 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs2816949; hg19: chr1-199997778; COSMIC: COSV52655530;