1-200120992-G-A

Position:

• chr1-200120992-G-A

Variant summary

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

The NM_205860.3(NR5A2):​c.1378+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,608,088 control chromosomes in the GnomAD database, including 63,449 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 0.26 (5472 hom., cov: 33)
  • Exomes 𝑓: 0.28 (57977 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1378+37G>A		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1378+37G>A		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.1240+37G>A		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.1162+37G>A		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39693 AN: 151996 Hom.: 5457 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.277 AC: 69146 AN: 249570 Hom.: 9859 AF XY: 0.276 AC XY: 37223 AN XY: 134890

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.280 AC: 407394 AN: 1455974 Hom.: 57977 Cov.: 29 AF XY: 0.280 AC XY: 202783 AN XY: 724564

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.261 AC: 39727 AN: 152114 Hom.: 5472 Cov.: 33 AF XY: 0.261 AC XY: 19419 AN XY: 74356

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.297

Alfa AF: 0.283 Hom.: 13027

Bravo AF: 0.262

Asia WGS AF: 0.281 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.39
DANN	Benign	0.49

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: rs3762398; hg19: chr1-200090120; COSMIC: COSV52656014;