rs11204894

Variant names:

• chr1-151820698-G-T
• rs11204894
• NM_005060.4:c.71-3418C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005060.4(RORC):​c.71-3418C>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
• Publications: 12 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=-0.85).
• 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 rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.71-3418C>A		intron_variant	Intron 2 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.8-3418C>A		intron_variant	Intron 1 of 9		NP_001001523.1
RORC	XM_006711484.5	c.233-3418C>A		intron_variant	Intron 3 of 11		XP_006711547.3
RORC	XM_047427201.1	c.8-3418C>A		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.71-3418C>A		intron_variant	Intron 2 of 10	1	NM_005060.4	ENSP00000327025.6

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

African (AFR) AF: 0.201 AC: 8346 AN: 41480

American (AMR) AF: 0.313 AC: 4791 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.129 AC: 666 AN: 5170

South Asian (SAS) AF: 0.120 AC: 578 AN: 4820

European-Finnish (FIN) AF: 0.290 AC: 3061 AN: 10560

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14656 AN: 67980

Other (OTH) AF: 0.224 AC: 472 AN: 2108

Alfa AF: 0.208 Hom.: 2064

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
PhyloP100		-0.28
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: rs11204894; hg19: chr1-151793174;