1-200111336-CAAAAAAA-CAAAAAA

Variant names:

• chr1-200111336-CA-C
• rs76894039
• NM_205860.3:c.1230+30delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_205860.3(NR5A2):​c.1230+30delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,296,592 control chromosomes in the GnomAD database, including 39 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0088 (6 hom., cov: 27)
  • Exomes 𝑓: 0.14 (33 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1230+30delA		intron_variant	Intron 6 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+16delA		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1092+16delA		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1014+16delA		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.00876 AC: 1107 AN: 126390 Hom.: 6 Cov.: 27

Gnomad AFR AF: 0.00310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00256

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00214

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0115

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.00810

GnomAD3 exomes AF: 0.210 AC: 21446 AN: 102246 Hom.: 13 AF XY: 0.214 AC XY: 11786 AN XY: 54958

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.250

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.137 AC: 159885 AN: 1170186 Hom.: 33 Cov.: 0 AF XY: 0.139 AC XY: 80556 AN XY: 579382

Gnomad4 AFR exome AF: 0.0952

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.00877 AC: 1109 AN: 126406 Hom.: 6 Cov.: 27 AF XY: 0.00929 AC XY: 564 AN XY: 60734

Gnomad4 AFR AF: 0.00315

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00256

Gnomad4 EAS AF: 0.00101

Gnomad4 SAS AF: 0.00215

Gnomad4 FIN AF: 0.0144

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.00810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs76894039; hg19: chr1-200080464;