Variant rs939595 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005060.4(RORC):c.1395+113T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 599,494 control chromosomes in the GnomAD database, including 124,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 31954 hom., cov: 31)

Exomes 𝑓: 0.64 ( 92911 hom. )

Consequence

RORC
NM_005060.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.91

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]

RORC links:

RORC (HGNC:):

RORC links:

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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=-0.97).

BP6

Variant 1-151811212-A-C is Benign according to our data. Variant chr1-151811212-A-C is described in ClinVar as [Benign]. Clinvar id is 2628210.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RORC	NM_005060.4 linkuse as main transcript	c.1395+113T>G	intron_variant	ENST00000318247.7	NP_005051.2	P51449-1Q6I9R9
RORC	NM_001001523.2 linkuse as main transcript	c.1332+113T>G	intron_variant		NP_001001523.1	P51449-2F1D8P6
RORC	XM_006711484.5 linkuse as main transcript	c.1557+113T>G	intron_variant		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7 linkuse as main transcript	c.1395+113T>G		intron_variant		1	NM_005060.4	ENSP00000327025.6		P51449-1

Frequencies

GnomAD3 genomes

AF:

0.645

AC:

97989

AN:

151876

Hom.:

31939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.642

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.617

GnomAD4 exome

AF:

0.641

AC:

286769

AN:

447500

Hom.:

92911

AF XY:

0.644

AC XY:

151531

AN XY:

235252

show subpopulations

Gnomad4 AFR exome

AF:

0.685

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.523

Gnomad4 EAS exome

AF:

0.725

Gnomad4 SAS exome

AF:

0.747

Gnomad4 FIN exome

AF:

0.623

Gnomad4 NFE exome

AF:

0.626

Gnomad4 OTH exome

AF:

0.621

GnomAD4 genome

AF:

0.645

AC:

98045

AN:

151994

Hom.:

31954

Cov.:

AF XY:

0.645

AC XY:

47937

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.773

Gnomad4 FIN

AF:

0.619

Gnomad4 NFE

AF:

0.628

Gnomad4 OTH

AF:

0.616

Alfa

AF:

0.618

Hom.:

46304

Bravo

AF:

0.647

Asia WGS

AF:

0.728

AC:

2533

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 submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.011

DANN

Benign

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over