chr1-200135844-A-C

Variant names:

• chr1-200135844-A-C
• rs10919814
• NM_205860.3:c.1378+14889A>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.1378+14889A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,168 control chromosomes in the GnomAD database, including 4,981 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 0.24 (4981 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.1378+14889A>C		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1240+14889A>C		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1162+14889A>C		intron	N/A	NP_001263393.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.1378+14889A>C		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.1240+14889A>C		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000544748.5	TSL:2	c.1162+14889A>C		intron	N/A	ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36490 AN: 152050 Hom.: 4968 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.240 AC: 36522 AN: 152168 Hom.: 4981 Cov.: 32 AF XY: 0.241 AC XY: 17900 AN XY: 74408

African (AFR) AF: 0.107 AC: 4424 AN: 41534

American (AMR) AF: 0.320 AC: 4885 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1184 AN: 5176

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4812

European-Finnish (FIN) AF: 0.261 AC: 2761 AN: 10590

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 20013 AN: 67986

Other (OTH) AF: 0.270 AC: 571 AN: 2114

Alfa AF: 0.282 Hom.: 8484

Bravo AF: 0.237

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		0.27
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: rs10919814; hg19: chr1-200104972; COSMIC: COSV107248069;