rs12069549

Variant names:

• chr1-200067011-C-T
• rs12069549
• NM_205860.3:c.1110+18193C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1110+18193C>T		intron_variant	Intron 5 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1110+18193C>T		intron_variant	Intron 5 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.972+18193C>T		intron_variant	Intron 4 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.894+18193C>T		intron_variant	Intron 4 of 6	2		ENSP00000439116.1

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

African (AFR) AF: 0.407 AC: 16897 AN: 41486

American (AMR) AF: 0.168 AC: 2563 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.188 AC: 976 AN: 5180

South Asian (SAS) AF: 0.128 AC: 617 AN: 4828

European-Finnish (FIN) AF: 0.134 AC: 1423 AN: 10602

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8778 AN: 67992

Other (OTH) AF: 0.195 AC: 411 AN: 2112

Alfa AF: 0.154 Hom.: 3613

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
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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