9-124481358-A-G

Position:

• chr9-124481358-A-G

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.*1400T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 140,454 control chromosomes in the GnomAD database, including 24,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (24865 hom., cov: 22)
  • Exomes 𝑓: 0.063 (1 hom.)
• Consequence: NR5A1 NM_004959.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.291

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=-0.89).
• BP6: Variant 9-124481358-A-G is Benign according to our data. Variant chr9-124481358-A-G is described in ClinVar as [Benign]. Clinvar id is 701815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A1	NM_004959.5	c.*1400T>C		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	c.*1400T>C		3_prime_UTR_variant	7/7	1	NM_004959.5	ENSP00000362690	P1
NR5A1	ENST00000620110.4	c.*1400T>C		3_prime_UTR_variant	6/6	5		ENSP00000483309

Frequencies

GnomAD3 genomes AF: 0.590 AC: 82843 AN: 140314 Hom.: 24824 Cov.: 22

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.585

GnomAD4 exome AF: 0.0625 AC: 3 AN: 48 Hom.: 1 Cov.: 0 AF XY: 0.107 AC XY: 3 AN XY: 28

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.591 AC: 82937 AN: 140406 Hom.: 24865 Cov.: 22 AF XY: 0.593 AC XY: 40268 AN XY: 67952

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.589

Alfa AF: 0.335 Hom.: 728

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.26

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: rs10283445; hg19: chr9-127243637;