1-200085949-G-T

Position:

• chr1-200085949-G-T

Variant summary

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

The NM_205860.3(NR5A2):​c.1111-25253G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,898 control chromosomes in the GnomAD database, including 21,104 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 0.53 (21104 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1111-25253G>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.1111-25253G>T		intron_variant		1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.973-25253G>T		intron_variant		1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.895-25253G>T		intron_variant		2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79778 AN: 151780 Hom.: 21084 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.526 AC: 79838 AN: 151898 Hom.: 21104 Cov.: 32 AF XY: 0.528 AC XY: 39172 AN XY: 74228

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.521

Alfa AF: 0.500 Hom.: 2573

Bravo AF: 0.529

Asia WGS AF: 0.522 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.93
DANN	Benign	0.31

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: rs2816928; hg19: chr1-200055077;