rs9826

Positions:

• chr1-151806423-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005060.4(RORC):​c.*1049A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 153,356 control chromosomes in the GnomAD database, including 7,758 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 0.30 (7684 hom., cov: 32)
  • Exomes 𝑓: 0.34 (74 hom.)
• Consequence: RORC NM_005060.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORC	NM_005060.4	c.*1049A>G		3_prime_UTR_variant	11/11	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.*1049A>G		3_prime_UTR_variant	10/10		NP_001001523.1
RORC	XM_006711484.5	c.*1049A>G		3_prime_UTR_variant	12/12		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247	c.*1049A>G		3_prime_UTR_variant	11/11	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45627 AN: 152082 Hom.: 7673 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.342 AC: 395 AN: 1154 Hom.: 74 Cov.: 0 AF XY: 0.343 AC XY: 201 AN XY: 586

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.300 AC: 45668 AN: 152202 Hom.: 7684 Cov.: 32 AF XY: 0.304 AC XY: 22586 AN XY: 74408

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.348

Alfa AF: 0.348 Hom.: 12760

Bravo AF: 0.293

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9826; hg19: chr1-151778899; COSMIC: COSV59092003; COSMIC: COSV59092003;