rs12078096

Positions:

• chr1-200160941-A-C
• chr1-200160941-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_205860.3(NR5A2):​c.1379-13022A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 151,984 control chromosomes in the GnomAD database, including 416 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 0.048 (416 hom., cov: 31)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1379-13022A>C		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1379-13022A>C		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.1241-13022A>C		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.1163-13022A>C		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7257 AN: 151866 Hom.: 415 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0478 AC: 7268 AN: 151984 Hom.: 416 Cov.: 31 AF XY: 0.0494 AC XY: 3672 AN XY: 74300

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.0204

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0319

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0123 Hom.: 13

Bravo AF: 0.0498

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.8
DANN	Benign	0.73

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: rs12078096; hg19: chr1-200130069;