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9-124482791-C-T

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

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 2.71
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.71 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
NR5A1NM_004959.5 linkuse as main transcriptc.1353G>A p.Leu451= synonymous_variant 7/7 ENST00000373588.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR5A1ENST00000373588.9 linkuse as main transcriptc.1353G>A p.Leu451= synonymous_variant 7/71 NM_004959.5 P1
NR5A1ENST00000620110.4 linkuse as main transcriptc.1233G>A p.Leu411= synonymous_variant 6/65
NR5A1ENST00000373587.3 linkuse as main transcriptc.705G>A p.Leu235= synonymous_variant 5/53

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0137
AC:
1939
AN:
141972
Hom.:
53
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0481
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00381
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00333
Gnomad NFE
AF:
0.0000455
Gnomad OTH
AF:
0.00922
GnomAD3 exomes
AF:
0.00339
AC:
792
AN:
233722
Hom.:
20
AF XY:
0.00245
AC XY:
310
AN XY:
126638
show subpopulations
Gnomad AFR exome
AF:
0.0489
Gnomad AMR exome
AF:
0.00184
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000343
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000192
Gnomad OTH exome
AF:
0.00155
GnomAD4 exome
AF:
0.00155
AC:
1972
AN:
1268576
Hom.:
37
Cov.:
38
AF XY:
0.00134
AC XY:
845
AN XY:
628318
show subpopulations
Gnomad4 AFR exome
AF:
0.0597
Gnomad4 AMR exome
AF:
0.00243
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000719
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000223
Gnomad4 OTH exome
AF:
0.00313
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0137
AC:
1946
AN:
142082
Hom.:
53
Cov.:
29
AF XY:
0.0139
AC XY:
950
AN XY:
68514
show subpopulations
Gnomad4 AFR
AF:
0.0481
Gnomad4 AMR
AF:
0.00380
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000455
Gnomad4 OTH
AF:
0.00911
Alfa
AF:
0.00491
Hom.:
10
Bravo
AF:
0.0150
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

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, 2015- -
Oligosynaptic infertility;C2751824:46,XY disorder of sex development Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 13, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
9.8
Dann
Benign
0.93

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: rs79833327; hg19: chr9-127245070; API