chr9-124482791-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_004959.5(NR5A1):c.1353G>A(p.Leu451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,410,658 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 53 hom., cov: 29)
Exomes 𝑓: 0.0016 ( 37 hom. )
Consequence
NR5A1
NM_004959.5 synonymous
NM_004959.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.71
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 9-124482791-C-T is Benign according to our data. Variant chr9-124482791-C-T is described in ClinVar as [Benign]. Clinvar id is 702077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.71 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR5A1 | NM_004959.5 | c.1353G>A | p.Leu451= | synonymous_variant | 7/7 | ENST00000373588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR5A1 | ENST00000373588.9 | c.1353G>A | p.Leu451= | synonymous_variant | 7/7 | 1 | NM_004959.5 | P1 | |
NR5A1 | ENST00000620110.4 | c.1233G>A | p.Leu411= | synonymous_variant | 6/6 | 5 | |||
NR5A1 | ENST00000373587.3 | c.705G>A | p.Leu235= | synonymous_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0137 AC: 1939AN: 141972Hom.: 53 Cov.: 29
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GnomAD3 exomes AF: 0.00339 AC: 792AN: 233722Hom.: 20 AF XY: 0.00245 AC XY: 310AN XY: 126638
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GnomAD4 exome AF: 0.00155 AC: 1972AN: 1268576Hom.: 37 Cov.: 38 AF XY: 0.00134 AC XY: 845AN XY: 628318
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GnomAD4 genome AF: 0.0137 AC: 1946AN: 142082Hom.: 53 Cov.: 29 AF XY: 0.0139 AC XY: 950AN XY: 68514
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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 submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Oligosynaptic infertility;C2751824:46,XY disorder of sex development Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at