rs2249172

chr1-200113827-G-Achr1-200113827-G-Cchr1-200113827-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_205860.3(NR5A2):c.1230+2506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,914 control chromosomes in the GnomAD database, including 14,707 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 0.43 (14707 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1230+2506G>A		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+2506G>A		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.1092+2506G>A		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.1014+2506G>A		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65983 AN: 151796 Hom.: 14700 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.435 AC: 66016 AN: 151914 Hom.: 14707 Cov.: 32 AF XY: 0.440 AC XY: 32664 AN XY: 74226

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.429

Alfa AF: 0.430 Hom.: 2179

Bravo AF: 0.432

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.50

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: rs2249172; hg19: chr1-200082955;