rs11578418

Variant names:

• chr1-151820508-G-A
• rs11578418
• NM_005060.4:c.71-3228C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

RORC Gene-Disease associations (from GenCC):

• autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.71-3228C>T		intron_variant	Intron 2 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.8-3228C>T		intron_variant	Intron 1 of 9		NP_001001523.1
RORC	XM_006711484.5	c.233-3228C>T		intron_variant	Intron 3 of 11		XP_006711547.3
RORC	XM_047427201.1	c.8-3228C>T		intron_variant	Intron 1 of 5		XP_047283157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.71-3228C>T		intron_variant	Intron 2 of 10	1	NM_005060.4	ENSP00000327025.6

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

African (AFR) AF: 0.158 AC: 6528 AN: 41420

American (AMR) AF: 0.0816 AC: 1247 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0986 AC: 342 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0384 AC: 185 AN: 4812

European-Finnish (FIN) AF: 0.0859 AC: 910 AN: 10598

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6548 AN: 67960

Other (OTH) AF: 0.113 AC: 238 AN: 2106

Alfa AF: 0.101 Hom.: 1007

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
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11578418; hg19: chr1-151792984;