rs3828057

chr1-151807701-C-T

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.458

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=-0.83).
• 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
RORC	NM_005060.4	c.1396-68G>A		intron_variant		ENST00000318247.7
RORC	NM_001001523.2	c.1333-68G>A		intron_variant
RORC	XM_006711484.5	c.1558-68G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7	c.1396-68G>A		intron_variant		1	NM_005060.4	P4

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54952 AN: 151992 Hom.: 10796 Cov.: 32

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

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

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

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 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

Other links and lift over

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