rs6693413

Variant names:

• chr1-151819834-G-A
• rs6693413
• NM_005060.4:c.71-2554C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151819834-G-A
• chr1-151819834-G-C
• chr1-151819834-G-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.71-2554C>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
• Publications: 5 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, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005060.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	NM_005060.4	MANE Select	c.71-2554C>T		intron	N/A	NP_005051.2
	RORC	NM_001001523.2		c.8-2554C>T		intron	N/A	NP_001001523.1	P51449-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	ENST00000318247.7	TSL:1 MANE Select	c.71-2554C>T		intron	N/A	ENSP00000327025.6	P51449-1
	RORC	ENST00000356728.11	TSL:1	c.8-2554C>T		intron	N/A	ENSP00000349164.6	P51449-2
	RORC	ENST00000859919.1		c.71-2554C>T		intron	N/A	ENSP00000529978.1

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

African (AFR) AF: 0.305 AC: 12611 AN: 41406

American (AMR) AF: 0.360 AC: 5491 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3464

East Asian (EAS) AF: 0.451 AC: 2319 AN: 5146

South Asian (SAS) AF: 0.432 AC: 2078 AN: 4810

European-Finnish (FIN) AF: 0.538 AC: 5675 AN: 10550

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.517 AC: 35111 AN: 67914

Other (OTH) AF: 0.435 AC: 918 AN: 2110

Alfa AF: 0.468 Hom.: 5726

Bravo AF: 0.415

Asia WGS AF: 0.442 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.64
PhyloP100		0.29
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: rs6693413; hg19: chr1-151792310;