1-200111335-C-T

Position:

• chr1-200111335-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.1230+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,202,218 control chromosomes in the GnomAD database, including 10,312 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 0.29 (2834 hom., cov: 14)
  • Exomes 𝑓: 0.24 (7478 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1230+14C>T		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+14C>T		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.1092+14C>T		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.1014+14C>T		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 23933 AN: 81952 Hom.: 2833 Cov.: 14

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.0596

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0128

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.356 AC: 45069 AN: 126484 Hom.: 5328 AF XY: 0.356 AC XY: 24663 AN XY: 69340

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.337

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.215

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.240 AC: 269317 AN: 1120262 Hom.: 7478 Cov.: 29 AF XY: 0.241 AC XY: 133990 AN XY: 556416

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.292 AC: 23941 AN: 81956 Hom.: 2834 Cov.: 14 AF XY: 0.281 AC XY: 11073 AN XY: 39358

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.0128

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.257

Alfa AF: 0.434 Hom.: 11327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.58

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: rs3828110; hg19: chr1-200080463; COSMIC: COSV52657968;