rs12069549

Positions:

• chr1-200067011-C-T

Variant summary

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

The NM_205860.3(NR5A2):​c.1110+18193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,168 control chromosomes in the GnomAD database, including 4,607 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 0.21 (4607 hom., cov: 33)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1110+18193C>T		intron_variant		ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1110+18193C>T		intron_variant		1	NM_205860.3	ENSP00000356331	A1
NR5A2	ENST00000236914.7	c.972+18193C>T		intron_variant		1		ENSP00000236914	A1
NR5A2	ENST00000544748.5	c.894+18193C>T		intron_variant		2		ENSP00000439116	P4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32606 AN: 152050 Hom.: 4592 Cov.: 33

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.215 AC: 32665 AN: 152168 Hom.: 4607 Cov.: 33 AF XY: 0.212 AC XY: 15740 AN XY: 74408

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.195

Alfa AF: 0.146 Hom.: 2431

Bravo AF: 0.225

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.82

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: rs12069549; hg19: chr1-200036139; COSMIC: COSV52647084;