rs2248967

Positions:

• chr1-200115765-G-A
• chr1-200115765-G-C
• chr1-200115765-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+4444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,656 control chromosomes in the GnomAD database, including 14,664 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 (14664 hom., cov: 30)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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 (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+4444G>A		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+4444G>A		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.1092+4444G>A		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.1014+4444G>A		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65809 AN: 151538 Hom.: 14656 Cov.: 30

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.434 AC: 65845 AN: 151656 Hom.: 14664 Cov.: 30 AF XY: 0.439 AC XY: 32545 AN XY: 74072

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.428

Alfa AF: 0.430 Hom.: 2961

Bravo AF: 0.432

Asia WGS AF: 0.540 AC: 1875 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	0.084
DANN	Benign	0.38

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: rs2248967; hg19: chr1-200084893;