rs11578418

chr1-151820508-G-A

Variant summary

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

The NM_005060.4(RORC):c.71-3228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,038 control chromosomes in the GnomAD database, including 962 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 0.11 (962 hom., cov: 31)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORC	NM_005060.4	c.71-3228C>T		intron_variant		ENST00000318247.7
RORC	NM_001001523.2	c.8-3228C>T		intron_variant
RORC	XM_006711484.5	c.233-3228C>T		intron_variant
RORC	XM_047427201.1	c.8-3228C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7	c.71-3228C>T		intron_variant		1	NM_005060.4	P4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16092 AN: 151920 Hom.: 964 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0892

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0386

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.106 AC: 16100 AN: 152038 Hom.: 962 Cov.: 31 AF XY: 0.105 AC XY: 7774 AN XY: 74322

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0816

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0384

Gnomad4 FIN AF: 0.0859

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0947 Hom.: 448

Bravo AF: 0.107

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.032
Dann	Benign	0.66

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: rs11578418; hg19: chr1-151792984;