1-200096087-C-T

Variant names:

• chr1-200096087-C-T
• rs2821320
• NM_205860.3:c.1111-15115C>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.1111-15115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,784 control chromosomes in the GnomAD database, including 13,373 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 0.40 (13373 hom., cov: 31)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1111-15115C>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.1111-15115C>T		intron_variant	Intron 5 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.973-15115C>T		intron_variant	Intron 4 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.895-15115C>T		intron_variant	Intron 4 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61211 AN: 151670 Hom.: 13336 Cov.: 31

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.404 AC: 61302 AN: 151784 Hom.: 13373 Cov.: 31 AF XY: 0.404 AC XY: 29988 AN XY: 74172

African (AFR) AF: 0.557 AC: 23052 AN: 41394

American (AMR) AF: 0.409 AC: 6231 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1233 AN: 3466

East Asian (EAS) AF: 0.568 AC: 2916 AN: 5130

South Asian (SAS) AF: 0.441 AC: 2120 AN: 4808

European-Finnish (FIN) AF: 0.304 AC: 3203 AN: 10528

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21321 AN: 67910

Other (OTH) AF: 0.338 AC: 711 AN: 2106

Alfa AF: 0.317 Hom.: 4541

Bravo AF: 0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2821320; hg19: chr1-200065215; COSMIC: COSV52647156;