chr1-151807701-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005060.4(RORC):​c.1396-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,539,496 control chromosomes in the GnomAD database, including 140,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 10796 hom., cov: 32)
Exomes 𝑓: 0.43 ( 129303 hom. )

Consequence

RORC
NM_005060.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.458
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 1-151807701-C-T is Benign according to our data. Variant chr1-151807701-C-T is described in ClinVar as [Benign]. Clinvar id is 2628172.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RORCNM_005060.4 linkuse as main transcriptc.1396-68G>A intron_variant ENST00000318247.7
RORCNM_001001523.2 linkuse as main transcriptc.1333-68G>A intron_variant
RORCXM_006711484.5 linkuse as main transcriptc.1558-68G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RORCENST00000318247.7 linkuse as main transcriptc.1396-68G>A intron_variant 1 NM_005060.4 P4P51449-1

Frequencies

GnomAD3 genomes
AF:
0.362
AC:
54952
AN:
151992
Hom.:
10796
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.252
Gnomad AMI
AF:
0.458
Gnomad AMR
AF:
0.274
Gnomad ASJ
AF:
0.302
Gnomad EAS
AF:
0.203
Gnomad SAS
AF:
0.374
Gnomad FIN
AF:
0.409
Gnomad MID
AF:
0.291
Gnomad NFE
AF:
0.454
Gnomad OTH
AF:
0.349
GnomAD4 exome
AF:
0.425
AC:
590296
AN:
1387388
Hom.:
129303
AF XY:
0.425
AC XY:
292460
AN XY:
688468
show subpopulations
Gnomad4 AFR exome
AF:
0.245
Gnomad4 AMR exome
AF:
0.237
Gnomad4 ASJ exome
AF:
0.319
Gnomad4 EAS exome
AF:
0.232
Gnomad4 SAS exome
AF:
0.373
Gnomad4 FIN exome
AF:
0.424
Gnomad4 NFE exome
AF:
0.455
Gnomad4 OTH exome
AF:
0.387
GnomAD4 genome
AF:
0.361
AC:
54955
AN:
152108
Hom.:
10796
Cov.:
32
AF XY:
0.354
AC XY:
26344
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.252
Gnomad4 AMR
AF:
0.274
Gnomad4 ASJ
AF:
0.302
Gnomad4 EAS
AF:
0.203
Gnomad4 SAS
AF:
0.374
Gnomad4 FIN
AF:
0.409
Gnomad4 NFE
AF:
0.454
Gnomad4 OTH
AF:
0.352
Alfa
AF:
0.424
Hom.:
7296
Bravo
AF:
0.346
Asia WGS
AF:
0.308
AC:
1073
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanNov 12, 2023This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.80
DANN
Benign
0.28

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: rs3828057; hg19: chr1-151780177; COSMIC: COSV59092182; COSMIC: COSV59092182; API