1-200041696-C-T

Position:

• chr1-200041696-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.202+1901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,008 control chromosomes in the GnomAD database, including 8,275 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 0.30 (8275 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.202+1901C>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.202+1901C>T		intron_variant		1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.65-2078C>T		intron_variant		1		ENSP00000236914.3
NR5A2	ENST00000474307.1	n.*419-2078C>T		intron_variant		1		ENSP00000436776.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45308 AN: 151890 Hom.: 8256 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.298 AC: 45332 AN: 152008 Hom.: 8275 Cov.: 32 AF XY: 0.312 AC XY: 23221 AN XY: 74318

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.287

Alfa AF: 0.314 Hom.: 6757

Bravo AF: 0.289

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs3790843; hg19: chr1-200010824;