rs11204894

chr1-151820698-G-T

Variant summary

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

The NM_005060.4(RORC):c.71-3418C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,080 control chromosomes in the GnomAD database, including 3,923 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 0.22 (3923 hom., cov: 32)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORC	NM_005060.4	c.71-3418C>A		intron_variant		ENST00000318247.7
RORC	NM_001001523.2	c.8-3418C>A		intron_variant
RORC	XM_006711484.5	c.233-3418C>A		intron_variant
RORC	XM_047427201.1	c.8-3418C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7	c.71-3418C>A		intron_variant		1	NM_005060.4	P4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33433 AN: 151962 Hom.: 3923 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33455 AN: 152080 Hom.: 3923 Cov.: 32 AF XY: 0.223 AC XY: 16563 AN XY: 74328

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.224

Alfa AF: 0.208 Hom.: 1886

Bravo AF: 0.222

Asia WGS AF: 0.162 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.1
Dann	Benign	0.70

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: rs11204894; hg19: chr1-151793174;