rs12041297

Variant names:

• chr1-200117296-A-C
• rs12041297
• NM_205860.3:c.1231-3512A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_205860.3(NR5A2):​c.1231-3512A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,284 control chromosomes in the GnomAD database, including 1,190 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 0.12 (1190 hom., cov: 33)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1231-3512A>C		intron_variant	Intron 6 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1231-3512A>C		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1093-3512A>C		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1015-3512A>C		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18069 AN: 152166 Hom.: 1188 Cov.: 33

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.119 AC: 18082 AN: 152284 Hom.: 1190 Cov.: 33 AF XY: 0.116 AC XY: 8660 AN XY: 74466

African (AFR) AF: 0.0719 AC: 2989 AN: 41566

American (AMR) AF: 0.102 AC: 1560 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3472

East Asian (EAS) AF: 0.0738 AC: 383 AN: 5192

South Asian (SAS) AF: 0.0829 AC: 400 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1429 AN: 10610

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10339 AN: 68002

Other (OTH) AF: 0.105 AC: 222 AN: 2114

Alfa AF: 0.137 Hom.: 2812

Bravo AF: 0.112

Asia WGS AF: 0.0760 AC: 262 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.8
DANN	Benign	0.53
PhyloP100		1.3
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: rs12041297; hg19: chr1-200086424; COSMIC: COSV52647361;