rs60535681

Variant names:

• chr1-200029176-G-A
• rs60535681
• ENST00000474307.1:n.208G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000474307.1(NR5A2):​n.208G>A variant causes a non coding transcript exon 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 ENST00000474307.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474307.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.64+1265G>A		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.64+1265G>A		intron	N/A	NP_003813.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000474307.1	TSL:1	n.208G>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000436776.1
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.64+1265G>A		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.64+1265G>A		intron	N/A	ENSP00000236914.3

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

GnomAD2 exomes AF: 0.0662 AC: 5238 AN: 79076 AF XY: 0.0607

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 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

African (AFR) AF: 0.316 AC: 1384 AN: 4380

American (AMR) AF: 0.0615 AC: 1193 AN: 19398

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 895 AN: 8894

East Asian (EAS) AF: 0.0377 AC: 82 AN: 2174

South Asian (SAS) AF: 0.0165 AC: 857 AN: 51948

European-Finnish (FIN) AF: 0.0639 AC: 720 AN: 11272

Middle Eastern (MID) AF: 0.116 AC: 299 AN: 2580

European-Non Finnish (NFE) AF: 0.0798 AC: 10355 AN: 129744

Other (OTH) AF: 0.0966 AC: 1087 AN: 11248

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

African (AFR) AF: 0.310 AC: 12822 AN: 41394

American (AMR) AF: 0.100 AC: 1530 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3466

East Asian (EAS) AF: 0.0388 AC: 199 AN: 5130

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4826

European-Finnish (FIN) AF: 0.0587 AC: 615 AN: 10484

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0780 AC: 5294 AN: 67890

Other (OTH) AF: 0.124 AC: 261 AN: 2108

Alfa AF: 0.112 Hom.: 313

Bravo AF: 0.153

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.4
DANN	Benign	0.93
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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