Variant 9-124500585-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004959.5(NR5A1):c.375G>A(p.Pro125Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,611,976 control chromosomes in the GnomAD database, including 3,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 1801 hom., cov: 33)

Exomes 𝑓: 0.0088 ( 1681 hom. )

Consequence

NR5A1
NM_004959.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.56

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 9-124500585-C-T is Benign according to our data. Variant chr9-124500585-C-T is described in ClinVar as [Benign]. Clinvar id is 259590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-124500585-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.56 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 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.375G>A	p.Pro125Pro	synonymous_variant	4/7	ENST00000373588.9	NP_004950.2	Q13285F1D8R8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NR5A1	ENST00000373588.9 linkuse as main transcript	c.375G>A	p.Pro125Pro	synonymous_variant	4/7	1	NM_004959.5	ENSP00000362690.4	Q13285
NR5A1	ENST00000620110.4 linkuse as main transcript	c.375G>A	p.Pro125Pro	synonymous_variant	4/6	5		ENSP00000483309.1	F1DAM0
NR5A1	ENST00000455734.1 linkuse as main transcript	c.375G>A	p.Pro125Pro	synonymous_variant	4/4	3		ENSP00000393245.1	Q5T6F6
NR5A1	ENST00000373587.3 linkuse as main transcript	c.40-313G>A		intron_variant		3		ENSP00000362689.3	Q5T6F7

Frequencies

GnomAD3 genomes

AF:

0.0843

AC:

12824

AN:

152146

Hom.:

1800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0313

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.0654

GnomAD3 exomes

AF:

0.0216

AC:

5183

AN:

240292

Hom.:

704

AF XY:

0.0165

AC XY:

2176

AN XY:

132046

show subpopulations

Gnomad AFR exome

AF:

0.306

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.000815

Gnomad EAS exome

AF:

0.00146

Gnomad SAS exome

AF:

0.000428

Gnomad FIN exome

AF:

0.0000482

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.00877

AC:

12796

AN:

1459712

Hom.:

1681

Cov.:

AF XY:

0.00759

AC XY:

5509

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000806

Gnomad4 SAS exome

AF:

0.000707

Gnomad4 FIN exome

AF:

0.000116

Gnomad4 NFE exome

AF:

0.000597

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0844

AC:

12846

AN:

152264

Hom.:

1801

Cov.:

AF XY:

0.0807

AC XY:

6009

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.0312

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0647

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0964

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 31787151) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.025

DANN

Benign

0.70

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