NM_205860.3:c.1231-268A>C

Variant names:

• chr1-200120540-A-C
• rs10919811
• NM_205860.3:c.1231-268A>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.1231-268A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,996 control chromosomes in the GnomAD database, including 14,027 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 0.43 (14027 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205860.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.1231-268A>C		intron	N/A	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.1093-268A>C		intron	N/A	NP_003813.1	F1D8R9
	NR5A2	NM_001276464.2		c.1015-268A>C		intron	N/A	NP_001263393.1	O00482-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.1231-268A>C		intron	N/A	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.1093-268A>C		intron	N/A	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000892175.1		c.1156-268A>C		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64932 AN: 151876 Hom.: 14001 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.428 AC: 64997 AN: 151996 Hom.: 14027 Cov.: 32 AF XY: 0.424 AC XY: 31464 AN XY: 74274

African (AFR) AF: 0.427 AC: 17689 AN: 41448

American (AMR) AF: 0.453 AC: 6920 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1530 AN: 5166

South Asian (SAS) AF: 0.348 AC: 1674 AN: 4816

European-Finnish (FIN) AF: 0.392 AC: 4126 AN: 10534

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29971 AN: 67968

Other (OTH) AF: 0.425 AC: 898 AN: 2114

Alfa AF: 0.449 Hom.: 1863

Bravo AF: 0.429

Asia WGS AF: 0.365 AC: 1267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.027
DANN	Benign	0.53
PhyloP100		-1.2
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: rs10919811; hg19: chr1-200089668;