1-200047018-T-C

Position:

• chr1-200047018-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_205860.3(NR5A2):​c.464-1154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,004 control chromosomes in the GnomAD database, including 16,950 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 0.43 (16950 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.464-1154T>C		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.464-1154T>C		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.326-1154T>C		intron_variant		1		A1
NR5A2	ENST00000367357.3	c.226-1154T>C		intron_variant		1
NR5A2	ENST00000544748.5	c.248-1154T>C		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65003 AN: 151886 Hom.: 16905 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.428 AC: 65089 AN: 152004 Hom.: 16950 Cov.: 32 AF XY: 0.420 AC XY: 31187 AN XY: 74302

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.0734

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.411

Alfa AF: 0.358 Hom.: 5605

Bravo AF: 0.444

Asia WGS AF: 0.187 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.81

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: rs2821367; hg19: chr1-200016146; COSMIC: COSV52647046; COSMIC: COSV52647046;