1-200111336-CAAAAAAA-CAAAAAAAAAA

Variant names:

• chr1-200111336-C-CAAA
• rs76894039
• NM_205860.3:c.1230+28_1230+30dupAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_205860.3(NR5A2):​c.1230+28_1230+30dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,405,432 control chromosomes in the GnomAD database, including 67 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0082 (23 hom., cov: 27)
  • Exomes 𝑓: 0.0028 (44 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00821 (1038/126472) while in subpopulation AFR AF= 0.0227 (791/34892). AF 95% confidence interval is 0.0214. There are 23 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1038 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1230+28_1230+30dupAAA		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+15_1230+16insAAA		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1092+15_1092+16insAAA		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1014+15_1014+16insAAA		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.00820 AC: 1037 AN: 126456 Hom.: 23 Cov.: 27

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.0445

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000417

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000825

Gnomad OTH AF: 0.00637

GnomAD3 exomes AF: 0.00539 AC: 551 AN: 102246 Hom.: 43 AF XY: 0.00493 AC XY: 271 AN XY: 54958

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.000604

Gnomad SAS exome AF: 0.00159

Gnomad FIN exome AF: 0.00355

Gnomad NFE exome AF: 0.00480

Gnomad OTH exome AF: 0.00800

GnomAD4 exome AF: 0.00281 AC: 3592 AN: 1278960 Hom.: 44 Cov.: 0 AF XY: 0.00270 AC XY: 1710 AN XY: 633042

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.0209

Gnomad4 EAS exome AF: 0.000455

Gnomad4 SAS exome AF: 0.00126

Gnomad4 FIN exome AF: 0.00228

Gnomad4 NFE exome AF: 0.00201

Gnomad4 OTH exome AF: 0.00497

GnomAD4 genome AF: 0.00821 AC: 1038 AN: 126472 Hom.: 23 Cov.: 27 AF XY: 0.00798 AC XY: 485 AN XY: 60772

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.0445

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000417

Gnomad4 NFE AF: 0.000825

Gnomad4 OTH AF: 0.00637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;