1-200174314-T-C

Variant summary

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

The NM_205860.3(NR5A2):c.*104T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,206,380 control chromosomes in the GnomAD database, including 187,440 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 0.56 (25057 hom., cov: 31)
  • Exomes 𝑓: 0.55 (162383 hom.)
• Consequence: NR5A2 NM_205860.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805

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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.*104T>C		3_prime_UTR_variant	8/8	ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.*104T>C		3_prime_UTR_variant	8/8	1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.*104T>C		3_prime_UTR_variant	7/7	1		A1
NR5A2	ENST00000544748.5	c.*104T>C		3_prime_UTR_variant	7/7	2		P4

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85526 AN: 151864 Hom.: 25050 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.567

GnomAD4 exome AF: 0.547 AC: 576568 AN: 1054398 Hom.: 162383 Cov.: 14 AF XY: 0.546 AC XY: 279619 AN XY: 512518

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.0838

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.563 AC: 85579 AN: 151982 Hom.: 25057 Cov.: 31 AF XY: 0.554 AC XY: 41166 AN XY: 74288

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.0873

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.563

Alfa AF: 0.556 Hom.: 30994

Bravo AF: 0.568

Asia WGS AF: 0.268 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	14
Dann	Benign	0.86

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: rs1060061; hg19: chr1-200143442;