1-200174314-T-C

Variant names:

• chr1-200174314-T-C
• rs1060061
• NM_205860.3:c.*104T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.55).
• 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 rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.*104T>C		3_prime_UTR_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.*104T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.*104T>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.*104T>C		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000439116.1

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

African (AFR) AF: 0.678 AC: 16017 AN: 23640

American (AMR) AF: 0.504 AC: 9110 AN: 18080

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 9599 AN: 15718

East Asian (EAS) AF: 0.0838 AC: 2709 AN: 32328

South Asian (SAS) AF: 0.415 AC: 14350 AN: 34604

European-Finnish (FIN) AF: 0.523 AC: 15961 AN: 30546

Middle Eastern (MID) AF: 0.579 AC: 2346 AN: 4050

European-Non Finnish (NFE) AF: 0.567 AC: 482375 AN: 851074

Other (OTH) AF: 0.543 AC: 24101 AN: 44358

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

African (AFR) AF: 0.664 AC: 27519 AN: 41448

American (AMR) AF: 0.529 AC: 8087 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3468

East Asian (EAS) AF: 0.0873 AC: 452 AN: 5176

South Asian (SAS) AF: 0.389 AC: 1872 AN: 4814

European-Finnish (FIN) AF: 0.510 AC: 5381 AN: 10558

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38413 AN: 67924

Other (OTH) AF: 0.563 AC: 1191 AN: 2114

Alfa AF: 0.561 Hom.: 71958

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
PhyloP100		0.81
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: rs1060061; hg19: chr1-200143442;