1-200174153-C-T

Variant names:

• chr1-200174153-C-T
• rs1060060
• NM_205860.3:c.1569C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_205860.3(NR5A2):​c.1569C>T​(p.Asn523Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,612,438 control chromosomes in the GnomAD database, including 74,786 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 0.32 (8011 hom., cov: 28)
  • Exomes 𝑓: 0.30 (66775 hom.)
• Consequence: NR5A2 NM_205860.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 22 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-2.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1569C>T	p.Asn523Asn	synonymous_variant	Exon 8 of 8	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1569C>T	p.Asn523Asn	synonymous_variant	Exon 8 of 8	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1431C>T	p.Asn477Asn	synonymous_variant	Exon 7 of 7	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1353C>T	p.Asn451Asn	synonymous_variant	Exon 7 of 7	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48562 AN: 151248 Hom.: 7996 Cov.: 28

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.320 AC: 80120 AN: 250526 AF XY: 0.313

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.534

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.299 AC: 436393 AN: 1461072 Hom.: 66775 Cov.: 40 AF XY: 0.297 AC XY: 215827 AN XY: 726808

African (AFR) AF: 0.351 AC: 11731 AN: 33452

American (AMR) AF: 0.356 AC: 15880 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7619 AN: 26102

East Asian (EAS) AF: 0.524 AC: 20771 AN: 39660

South Asian (SAS) AF: 0.251 AC: 21648 AN: 86166

European-Finnish (FIN) AF: 0.292 AC: 15582 AN: 53386

Middle Eastern (MID) AF: 0.287 AC: 1653 AN: 5766

European-Non Finnish (NFE) AF: 0.291 AC: 323424 AN: 1111566

Other (OTH) AF: 0.300 AC: 18085 AN: 60372

GnomAD4 genome AF: 0.321 AC: 48608 AN: 151366 Hom.: 8011 Cov.: 28 AF XY: 0.323 AC XY: 23910 AN XY: 73942

African (AFR) AF: 0.352 AC: 14481 AN: 41178

American (AMR) AF: 0.351 AC: 5340 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2670 AN: 5116

South Asian (SAS) AF: 0.266 AC: 1276 AN: 4792

European-Finnish (FIN) AF: 0.286 AC: 2993 AN: 10448

Middle Eastern (MID) AF: 0.317 AC: 92 AN: 290

European-Non Finnish (NFE) AF: 0.291 AC: 19738 AN: 67838

Other (OTH) AF: 0.299 AC: 627 AN: 2096

Alfa AF: 0.301 Hom.: 11069

Bravo AF: 0.330

Asia WGS AF: 0.380 AC: 1320 AN: 3478

EpiCase AF: 0.287

EpiControl AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.029
DANN	Benign	0.66
PhyloP100		-2.6
Mutation Taster		=99/1	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: rs1060060; hg19: chr1-200143281; COSMIC: COSV52645455;