rs10919814

Variant names:

• chr1-200135844-A-C
• rs10919814
• NM_205860.3:c.1378+14889A>C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1378+14889A>C		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+14889A>C		intron_variant	Intron 7 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1240+14889A>C		intron_variant	Intron 6 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1162+14889A>C		intron_variant	Intron 6 of 6	2		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

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.270

Alfa AF: 0.287 Hom.: 6832

Bravo AF: 0.237

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs10919814; hg19: chr1-200104972;