Genetic Variant NR5A2:c.1230+29_1230+30dupAA (chr1-200111336-C-CAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_205860.3(NR5A2):c.1230+29_1230+30dupAA 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.881

Variant links:

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]

NR5A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
NR5A2	NM_205860.3 link	c.1230+29_1230+30dupAA		intron_variant	Intron 6 of 7	ENST00000367362.8	NP_995582.1	O00482-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NR5A2	ENST00000367362.8 link	c.1230+15_1230+16insAA	intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3	O00482-1
NR5A2	ENST00000236914.7 link	c.1092+15_1092+16insAA	intron_variant	Intron 5 of 6	1		ENSP00000236914.3	O00482-2
NR5A2	ENST00000544748.5 link	c.1014+15_1014+16insAA	intron_variant	Intron 5 of 6	2		ENSP00000439116.1	O00482-4

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

16297

AN:

126258

Hom.:

1136

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0763

AC XY:

47498

AN XY:

622444

show subpopulations

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.:

AF XY:

0.124

AC XY:

7494

AN XY:

60674

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

1-200111336-CAAAAAAA-CAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over