1-151806207-C-T

Position:

• chr1-151806207-C-T

Variant summary

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

The NM_005060.4(RORC):​c.*1265G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,836 control chromosomes in the GnomAD database, including 27,390 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 0.59 (27153 hom., cov: 30)
  • Exomes 𝑓: 0.66 (237 hom.)
• Consequence: RORC NM_005060.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORC	NM_005060.4	c.*1265G>A		3_prime_UTR_variant	11/11	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.*1265G>A		3_prime_UTR_variant	10/10		NP_001001523.1
RORC	XM_006711484.5	c.*1265G>A		3_prime_UTR_variant	12/12		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.*1265G>A		3_prime_UTR_variant	11/11	1	NM_005060.4	ENSP00000327025	P4

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89722 AN: 151648 Hom.: 27148 Cov.: 30

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.658 AC: 705 AN: 1072 Hom.: 237 Cov.: 0 AF XY: 0.660 AC XY: 355 AN XY: 538

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.591 AC: 89760 AN: 151764 Hom.: 27153 Cov.: 30 AF XY: 0.582 AC XY: 43193 AN XY: 74164

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.563

Alfa AF: 0.616 Hom.: 28171

Bravo AF: 0.580

Asia WGS AF: 0.478 AC: 1661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9017; hg19: chr1-151778683;