chr1-200132353-G-A

Variant names:

• chr1-200132353-G-A
• rs2816959
• NM_205860.3:c.1378+11398G>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.1378+11398G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,146 control chromosomes in the GnomAD database, including 56,570 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 0.86 (56570 hom., cov: 31)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1378+11398G>A		intron_variant	Intron 7 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1378+11398G>A		intron_variant	Intron 7 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1240+11398G>A		intron_variant	Intron 6 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1162+11398G>A		intron_variant	Intron 6 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131044 AN: 152028 Hom.: 56521 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.862 AC: 131152 AN: 152146 Hom.: 56570 Cov.: 31 AF XY: 0.860 AC XY: 63976 AN XY: 74382

African (AFR) AF: 0.874 AC: 36267 AN: 41504

American (AMR) AF: 0.905 AC: 13849 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3084 AN: 3470

East Asian (EAS) AF: 0.976 AC: 5050 AN: 5176

South Asian (SAS) AF: 0.846 AC: 4075 AN: 4816

European-Finnish (FIN) AF: 0.805 AC: 8510 AN: 10570

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57480 AN: 67990

Other (OTH) AF: 0.860 AC: 1817 AN: 2112

Alfa AF: 0.853 Hom.: 246639

Bravo AF: 0.872

Asia WGS AF: 0.908 AC: 3157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.010
DANN	Benign	0.44
PhyloP100		-1.3
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: rs2816959; hg19: chr1-200101481;