1-200064641-A-G

Position:

• chr1-200064641-A-G

Variant summary

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

The NM_205860.3(NR5A2):​c.1110+15823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,010 control chromosomes in the GnomAD database, including 11,867 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 0.36 (11867 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1110+15823A>G		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1110+15823A>G		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.972+15823A>G		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.894+15823A>G		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55035 AN: 151892 Hom.: 11829 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.363 AC: 55119 AN: 152010 Hom.: 11867 Cov.: 32 AF XY: 0.359 AC XY: 26676 AN XY: 74312

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.337

Alfa AF: 0.307 Hom.: 1648

Bravo AF: 0.375

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.63

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: rs2821388; hg19: chr1-200033769;