rs6693413

chr1-151819834-G-Achr1-151819834-G-Cchr1-151819834-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.71-2554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,860 control chromosomes in the GnomAD database, including 15,147 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 0.44 (15147 hom., cov: 30)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORC	NM_005060.4	c.71-2554C>T		intron_variant		ENST00000318247.7
RORC	NM_001001523.2	c.8-2554C>T		intron_variant
RORC	XM_006711484.5	c.233-2554C>T		intron_variant
RORC	XM_047427201.1	c.8-2554C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7	c.71-2554C>T		intron_variant		1	NM_005060.4	P4

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66065 AN: 151740 Hom.: 15145 Cov.: 30

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.435 AC: 66086 AN: 151860 Hom.: 15147 Cov.: 30 AF XY: 0.434 AC XY: 32215 AN XY: 74210

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.435

Alfa AF: 0.482 Hom.: 2958

Bravo AF: 0.415

Asia WGS AF: 0.442 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.0
Dann	Benign	0.64

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: rs6693413; hg19: chr1-151792310;