9-124482584-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004959.5(NR5A1):c.*173del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25787 hom., cov: 0)
  • Exomes 𝑓: 0.51 (86361 hom.)
• Consequence: NR5A1 NM_004959.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.824

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 -10 ACMG points.

• BP6: Variant 9-124482584-AC-A is Benign according to our data. Variant chr9-124482584-AC-A is described in ClinVar as [Benign]. Clinvar id is 1263592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A1	NM_004959.5	c.*173del		3_prime_UTR_variant	7/7	ENST00000373588.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A1	ENST00000373588.9	c.*173del		3_prime_UTR_variant	7/7	1	NM_004959.5	P1
NR5A1	ENST00000620110.4	c.*173del		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86378 AN: 151638 Hom.: 25744 Cov.: 0

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.513 AC: 321065 AN: 625384 Hom.: 86361 Cov.: 0 AF XY: 0.515 AC XY: 166947 AN XY: 324026

Gnomad4 AFR exome AF: 0.722

Gnomad4 AMR exome AF: 0.696

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.829

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.523

GnomAD4 genome AF: 0.570 AC: 86480 AN: 151754 Hom.: 25787 Cov.: 0 AF XY: 0.570 AC XY: 42267 AN XY: 74136

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.562

Alfa AF: 0.517 Hom.: 2596

Bravo AF: 0.587

Asia WGS AF: 0.701 AC: 2423 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

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Computational scores

Source: dbNSFP v4.3

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: rs5900617; hg19: chr9-127244863;