chr1-200080174-T-A

Variant names:

• chr1-200080174-T-A
• rs6658424
• NM_205860.3:c.1111-31028T>A

Variant summary

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

The NM_205860.3(NR5A2):​c.1111-31028T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,942 control chromosomes in the GnomAD database, including 6,267 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 0.29 (6267 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1111-31028T>A		intron_variant	Intron 5 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1111-31028T>A		intron_variant	Intron 5 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.973-31028T>A		intron_variant	Intron 4 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.895-31028T>A		intron_variant	Intron 4 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43429 AN: 151826 Hom.: 6266 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43440 AN: 151942 Hom.: 6267 Cov.: 32 AF XY: 0.284 AC XY: 21084 AN XY: 74242

African (AFR) AF: 0.287 AC: 11915 AN: 41448

American (AMR) AF: 0.269 AC: 4108 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1281 AN: 3472

East Asian (EAS) AF: 0.191 AC: 988 AN: 5166

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4810

European-Finnish (FIN) AF: 0.299 AC: 3142 AN: 10514

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.292 AC: 19848 AN: 67966

Other (OTH) AF: 0.298 AC: 628 AN: 2110

Alfa AF: 0.292 Hom.: 794

Bravo AF: 0.285

Asia WGS AF: 0.220 AC: 764 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		-0.90
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: rs6658424; hg19: chr1-200049302;