1-200111336-CAAAAAAA-CAAAAAAAAAAAA

Variant names:

• chr1-200111336-C-CAAAAA
• rs76894039
• NM_205860.3:c.1230+26_1230+30dupAAAAA

Variant summary

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

The NM_205860.3(NR5A2):​c.1230+26_1230+30dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (107 hom., cov: 27)
  • Exomes 𝑓: 0.00056 (13 hom.)
  • Failed GnomAD Quality Control
• 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_exome allele frequency = 0.00056 (717/1281054) while in subpopulation AFR AF= 0.0225 (591/26210). AF 95% confidence interval is 0.021. There are 13 homozygotes in gnomad4_exome. There are 308 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 717 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1230+26_1230+30dupAAAAA		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+16insAAAAA		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1092+15_1092+16insAAAAA		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1014+15_1014+16insAAAAA		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2387 AN: 126372 Hom.: 107 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00649

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00107

Gnomad FIN AF: 0.000139

Gnomad MID AF: 0.0154

Gnomad NFE AF: 0.000137

Gnomad OTH AF: 0.0150

GnomAD4 exome AF: 0.000560 AC: 717 AN: 1281054 Hom.: 13 Cov.: 0 AF XY: 0.000486 AC XY: 308 AN XY: 634026

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.000541

Gnomad4 ASJ exome AF: 0.0000497

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000465

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0189 AC: 2387 AN: 126388 Hom.: 107 Cov.: 27 AF XY: 0.0181 AC XY: 1098 AN XY: 60732

Gnomad4 AFR AF: 0.0650

Gnomad4 AMR AF: 0.00649

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000806

Gnomad4 FIN AF: 0.000139

Gnomad4 NFE AF: 0.000138

Gnomad4 OTH AF: 0.0150

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;