Variant chr9-124482676-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004959.5(NR5A1):c.*82C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,269,752 control chromosomes in the GnomAD database, including 163,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25776 hom., cov: 31)

Exomes 𝑓: 0.47 ( 137763 hom. )

Consequence

NR5A1
NM_004959.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.188

Variant links:

Genes affected

NR5A1 (HGNC:7983): (nuclear receptor subfamily 5 group A member 1) The protein encoded by this gene is a transcriptional activator involved in sex determination. The encoded protein binds DNA as a monomer. Defects in this gene are a cause of XY sex reversal with or without adrenal failure as well as adrenocortical insufficiency without ovarian defect. [provided by RefSeq, Jul 2008]

NR5A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-124482676-G-A is Benign according to our data. Variant chr9-124482676-G-A is described in ClinVar as [Benign]. Clinvar id is 701816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-124482676-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A1	NM_004959.5 linkuse as main transcript	c.*82C>T		3_prime_UTR_variant	7/7	ENST00000373588.9	NP_004950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR5A1	ENST00000373588.9 linkuse as main transcript	c.*82C>T		3_prime_UTR_variant	7/7	1	NM_004959.5	ENSP00000362690	P1
NR5A1	ENST00000620110.4 linkuse as main transcript	c.*82C>T		3_prime_UTR_variant	6/6	5		ENSP00000483309

Frequencies

GnomAD3 genomes

AF:

0.569

AC:

86290

AN:

151588

Hom.:

25733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.558

GnomAD4 exome

AF:

0.473

AC:

528827

AN:

1118054

Hom.:

137763

Cov.:

AF XY:

0.476

AC XY:

265951

AN XY:

558830

show subpopulations

Gnomad4 AFR exome

AF:

0.723

Gnomad4 AMR exome

AF:

0.693

Gnomad4 ASJ exome

AF:

0.469

Gnomad4 EAS exome

AF:

0.819

Gnomad4 SAS exome

AF:

0.578

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.435

Gnomad4 OTH exome

AF:

0.498

GnomAD4 genome

AF:

0.569

AC:

86389

AN:

151698

Hom.:

25776

Cov.:

AF XY:

0.570

AC XY:

42223

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.721

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.770

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.476

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.490

Hom.:

29297

Bravo

AF:

0.588

Asia WGS

AF:

0.700

AC:

2425

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 23096908, 27884173, 29090230) -

Oligosynaptic infertility;C2751824:46,XY disorder of sex development

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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

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