rs12030974

chr1-151825819-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005060.4(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 NM_005060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.628

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
RORC	NM_005060.4	c.70+3610C>T		intron_variant		ENST00000318247.7
RORC	NM_001001523.2	c.7+111C>T		intron_variant
RORC	XM_006711484.5	c.232+3610C>T		intron_variant
RORC	XM_047427201.1	c.7+111C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7	c.70+3610C>T		intron_variant		1	NM_005060.4	P4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28000 AN: 151992 Hom.: 3440 Cov.: 32

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

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.: 32 AF XY: 0.188 AC XY: 13990 AN XY: 74336

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

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

Other links and lift over

dbSNP: rs12030974; hg19: chr1-151798295; COSMIC: COSV59092111;