Variant rs12030974 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000318247.7(RORC):c.70+3610C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,299,052 control chromosomes in the GnomAD database, including 36,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 3442 hom., cov: 32)

Exomes 𝑓: 0.23 ( 33496 hom. )

Consequence

RORC
ENST00000318247.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.628

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:

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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=-0.77).

BP6

Variant 1-151825819-G-A is Benign according to our data. Variant chr1-151825819-G-A is described in ClinVar as [Benign]. Clinvar id is 2628168.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RORC	NM_005060.4 linkuse as main transcript	c.70+3610C>T	intron_variant	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2 linkuse as main transcript	c.7+111C>T	intron_variant		NP_001001523.1
RORC	XM_006711484.5 linkuse as main transcript	c.232+3610C>T	intron_variant		XP_006711547.3
RORC	XM_047427201.1 linkuse as main transcript	c.7+111C>T	intron_variant		XP_047283157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7 linkuse as main transcript	c.70+3610C>T		intron_variant		1	NM_005060.4	ENSP00000327025	P4	P51449-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28000

AN:

151992

Hom.:

3440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.227

AC:

260230

AN:

1146944

Hom.:

33496

AF XY:

0.234

AC XY:

134879

AN XY:

576902

show subpopulations

Gnomad4 AFR exome

AF:

0.0398

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.184

AC:

27995

AN:

152108

Hom.:

3442

Cov.:

AF XY:

0.188

AC XY:

13990

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0455

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.186

Hom.:

573

Bravo

AF:

0.187

Asia WGS

AF:

0.317

AC:

1100

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 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.3

DANN

Benign

0.67

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