1-200111336-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_205860.3(NR5A2):c.1230+29_1230+30dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 1,383,324 control chromosomes in the GnomAD database, including 1,856 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1138 hom., cov: 27)
  • Exomes 𝑓: 0.079 (718 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 1-200111336-C-CAA is Benign according to our data. Variant chr1-200111336-C-CAA is described in ClinVar as [Benign]. Clinvar id is 403261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1230+29_1230+30dup		intron_variant		ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+29_1230+30dup		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.1092+29_1092+30dup		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.1014+29_1014+30dup		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 16297 AN: 126258 Hom.: 1136 Cov.: 27

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0420

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00582

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.0480 AC: 4906 AN: 102246 Hom.: 397 AF XY: 0.0441 AC XY: 2426 AN XY: 54958

Gnomad AFR exome AF: 0.0838

Gnomad AMR exome AF: 0.0411

Gnomad ASJ exome AF: 0.0673

Gnomad EAS exome AF: 0.0116

Gnomad SAS exome AF: 0.0194

Gnomad FIN exome AF: 0.0400

Gnomad NFE exome AF: 0.0555

Gnomad OTH exome AF: 0.0512

GnomAD4 exome AF: 0.0787 AC: 98940 AN: 1257050 Hom.: 718 Cov.: 0 AF XY: 0.0763 AC XY: 47498 AN XY: 622444

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.0975

Gnomad4 EAS exome AF: 0.0124

Gnomad4 SAS exome AF: 0.0274

Gnomad4 FIN exome AF: 0.0583

Gnomad4 NFE exome AF: 0.0853

Gnomad4 OTH exome AF: 0.0759

GnomAD4 genome AF: 0.129 AC: 16299 AN: 126274 Hom.: 1138 Cov.: 27 AF XY: 0.124 AC XY: 7494 AN XY: 60674

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0997

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.00583

Gnomad4 SAS AF: 0.0436

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.123

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, outside ROI -

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;