1-200045432-C-T

Variant names:

• chr1-200045432-C-T
• rs41300849
• NM_205860.3:c.322-11C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_205860.3(NR5A2):​c.322-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 1,562,174 control chromosomes in the GnomAD database, including 6,308 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 0.081 (533 hom., cov: 33)
  • Exomes 𝑓: 0.087 (5775 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Scores: Splicing: ADA: 0.3595
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.322-11C>T		intron_variant	Intron 3 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.322-11C>T		intron_variant	Intron 3 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.184-11C>T		intron_variant	Intron 2 of 6	1		ENSP00000236914.3
NR5A2	ENST00000367357.3	c.82-11C>T		intron_variant	Intron 1 of 3	1		ENSP00000356326.3
NR5A2	ENST00000544748.5	c.106-11C>T		intron_variant	Intron 2 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12321 AN: 152064 Hom.: 532 Cov.: 33

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0676

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0825

GnomAD2 exomes AF: 0.0730 AC: 15401 AN: 210846 AF XY: 0.0732

Gnomad AFR exome AF: 0.0728

Gnomad AMR exome AF: 0.0412

Gnomad ASJ exome AF: 0.0675

Gnomad EAS exome AF: 0.0177

Gnomad FIN exome AF: 0.0544

Gnomad NFE exome AF: 0.0961

Gnomad OTH exome AF: 0.0783

GnomAD4 exome AF: 0.0869 AC: 122505 AN: 1409992 Hom.: 5775 Cov.: 29 AF XY: 0.0863 AC XY: 60489 AN XY: 700852

African (AFR) AF: 0.0663 AC: 2019 AN: 30440

American (AMR) AF: 0.0460 AC: 1535 AN: 33380

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 1552 AN: 24034

East Asian (EAS) AF: 0.0216 AC: 827 AN: 38346

South Asian (SAS) AF: 0.0577 AC: 4508 AN: 78152

European-Finnish (FIN) AF: 0.0582 AC: 3049 AN: 52376

Middle Eastern (MID) AF: 0.0416 AC: 231 AN: 5550

European-Non Finnish (NFE) AF: 0.0953 AC: 103879 AN: 1089612

Other (OTH) AF: 0.0844 AC: 4905 AN: 58102

GnomAD4 genome AF: 0.0810 AC: 12332 AN: 152182 Hom.: 533 Cov.: 33 AF XY: 0.0776 AC XY: 5775 AN XY: 74420

African (AFR) AF: 0.0729 AC: 3026 AN: 41508

American (AMR) AF: 0.0686 AC: 1049 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 234 AN: 3464

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5184

South Asian (SAS) AF: 0.0576 AC: 278 AN: 4826

European-Finnish (FIN) AF: 0.0507 AC: 538 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6805 AN: 67976

Other (OTH) AF: 0.0826 AC: 174 AN: 2106

Alfa AF: 0.0886 Hom.: 185

Bravo AF: 0.0798

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Benign	0.80
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.36
dbscSNV1_RF	Benign	0.54
SpliceAI score (max)		0.010		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: rs41300849; hg19: chr1-200014560; COSMIC: COSV107248066; COSMIC: COSV107248066;