9-124482676-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.188

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]

ACMG classification

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
NR5A1	NM_004959.5	c.*82C>T		3_prime_UTR_variant	7/7	ENST00000373588.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86290 AN: 151588 Hom.: 25733 Cov.: 31

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

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

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

Submissions by phenotype

not provided Benign:1

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

Invitae

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

Other links and lift over

dbSNP: rs915034; hg19: chr9-127244955;