rs60535681

Positions:

• chr1-200029176-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.64+1265G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 393,388 control chromosomes in the GnomAD database, including 3,203 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 0.14 (2320 hom., cov: 31)
  • Exomes 𝑓: 0.070 (883 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.64+1265G>A		intron_variant		ENST00000367362.8
NR5A2	NM_003822.5	c.64+1265G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.64+1265G>A		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.64+1265G>A		intron_variant		1		A1
NR5A2	ENST00000447034.1	c.29+1265G>A		intron_variant		1
NR5A2	ENST00000474307.1	c.208G>A	p.Ala70Thr	missense_variant, NMD_transcript_variant	2/3	1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21211 AN: 151640 Hom.: 2305 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.0662 AC: 5238 AN: 79076 Hom.: 278 AF XY: 0.0607 AC XY: 2760 AN XY: 45478

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0397

Gnomad SAS exome AF: 0.0155

Gnomad FIN exome AF: 0.0650

Gnomad NFE exome AF: 0.0814

Gnomad OTH exome AF: 0.0850

GnomAD4 exome AF: 0.0698 AC: 16872 AN: 241638 Hom.: 883 Cov.: 0 AF XY: 0.0627 AC XY: 8847 AN XY: 141204

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.0615

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0377

Gnomad4 SAS exome AF: 0.0165

Gnomad4 FIN exome AF: 0.0639

Gnomad4 NFE exome AF: 0.0798

Gnomad4 OTH exome AF: 0.0966

GnomAD4 genome AF: 0.140 AC: 21247 AN: 151750 Hom.: 2320 Cov.: 31 AF XY: 0.136 AC XY: 10091 AN XY: 74166

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0388

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.124

Alfa AF: 0.107 Hom.: 282

Bravo AF: 0.153

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.4
DANN	Benign	0.93

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: rs60535681; hg19: chr1-199998304; COSMIC: COSV52644633;