rs3790515

Variant names:

• chr1-151813896-C-T
• rs3790515
• NM_005060.4:c.934-276G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005060.4(RORC):​c.934-276G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 424,048 control chromosomes in the GnomAD database, including 4,182 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2480 hom., cov: 33)
  • Exomes 𝑓: 0.10 (1702 hom.)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.934-276G>A		intron_variant	Intron 6 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.871-276G>A		intron_variant	Intron 5 of 9		NP_001001523.1
RORC	XM_006711484.5	c.1096-276G>A		intron_variant	Intron 7 of 11		XP_006711547.3
RORC	XM_047427201.1	c.871-194G>A		intron_variant	Intron 5 of 5		XP_047283157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.934-276G>A		intron_variant	Intron 6 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23378 AN: 152024 Hom.: 2472 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.101 AC: 27385 AN: 271906 Hom.: 1702 Cov.: 0 AF XY: 0.0983 AC XY: 14009 AN XY: 142484

African (AFR) AF: 0.285 AC: 2532 AN: 8874

American (AMR) AF: 0.0863 AC: 947 AN: 10976

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 636 AN: 8512

East Asian (EAS) AF: 0.157 AC: 2798 AN: 17830

South Asian (SAS) AF: 0.0673 AC: 1963 AN: 29156

European-Finnish (FIN) AF: 0.162 AC: 2616 AN: 16110

Middle Eastern (MID) AF: 0.0627 AC: 78 AN: 1244

European-Non Finnish (NFE) AF: 0.0859 AC: 14023 AN: 163298

Other (OTH) AF: 0.113 AC: 1792 AN: 15906

GnomAD4 genome AF: 0.154 AC: 23420 AN: 152142 Hom.: 2480 Cov.: 33 AF XY: 0.155 AC XY: 11519 AN XY: 74372

African (AFR) AF: 0.291 AC: 12077 AN: 41472

American (AMR) AF: 0.103 AC: 1573 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.162 AC: 839 AN: 5170

South Asian (SAS) AF: 0.0732 AC: 353 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2032 AN: 10588

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0869 AC: 5907 AN: 68010

Other (OTH) AF: 0.123 AC: 259 AN: 2112

Alfa AF: 0.102 Hom.: 668

Bravo AF: 0.156

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.60
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3790515; hg19: chr1-151786372;