rs139551639
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_005060.4(RORC):c.1070C>T(p.Ala357Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
RORC
NM_005060.4 missense
NM_005060.4 missense
Scores
5
8
4
Clinical Significance
Conservation
PhyloP100: 1.76
Genes affected
RORC (HGNC:10260): (RAR related orphan receptor C) The protein encoded by this gene is a DNA-binding transcription factor and is a member of the NR1 subfamily of nuclear hormone receptors. The specific functions of this protein are not known; however, studies of a similar gene in mice have shown that this gene may be essential for lymphoid organogenesis and may play an important regulatory role in thymopoiesis. In addition, studies in mice suggest that the protein encoded by this gene may inhibit the expression of Fas ligand and IL2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.02216354).
BP6
?
Variant 1-151813343-G-A is Benign according to our data. Variant chr1-151813343-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542374.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RORC | NM_005060.4 | c.1070C>T | p.Ala357Val | missense_variant | 8/11 | ENST00000318247.7 | |
RORC | NM_001001523.2 | c.1007C>T | p.Ala336Val | missense_variant | 7/10 | ||
RORC | XM_006711484.5 | c.1232C>T | p.Ala411Val | missense_variant | 9/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RORC | ENST00000318247.7 | c.1070C>T | p.Ala357Val | missense_variant | 8/11 | 1 | NM_005060.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000618 AC: 94AN: 152124Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
94
AN:
152124
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251390Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135850
GnomAD3 exomes
AF:
AC:
39
AN:
251390
Hom.:
AF XY:
AC XY:
12
AN XY:
135850
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461690Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 727194
GnomAD4 exome
AF:
AC:
68
AN:
1461690
Hom.:
Cov.:
30
AF XY:
AC XY:
24
AN XY:
727194
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000624 AC: 95AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45AN XY: 74430
GnomAD4 genome
?
AF:
AC:
95
AN:
152242
Hom.:
Cov.:
32
AF XY:
AC XY:
45
AN XY:
74430
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
6
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
21
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
1.3
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at