chr9-124482676-G-A

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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

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 UniProt
NR5A1NM_004959.5 linkuse as main transcriptc.*82C>T 3_prime_UTR_variant 7/7 ENST00000373588.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR5A1ENST00000373588.9 linkuse as main transcriptc.*82C>T 3_prime_UTR_variant 7/71 NM_004959.5 P1
NR5A1ENST00000620110.4 linkuse as main transcriptc.*82C>T 3_prime_UTR_variant 6/65

Frequencies

GnomAD3 genomes
AF:
0.569
AC:
86290
AN:
151588
Hom.:
25733
Cov.:
31
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.:
17
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.:
31
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015This 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 submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs915034; hg19: chr9-127244955; API