rs7546811

Variant names:

• chr1-151820366-G-A
• rs7546811
• NM_005060.4:c.71-3086C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151820366-G-A
• chr1-151820366-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005060.4(RORC):​c.71-3086C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 152,224 control chromosomes in the GnomAD database, including 129 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 0.022 (129 hom., cov: 31)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0744 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	NM_005060.4	MANE Select	c.71-3086C>T		intron	N/A	NP_005051.2
	RORC	NM_001001523.2		c.8-3086C>T		intron	N/A	NP_001001523.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	ENST00000318247.7	TSL:1 MANE Select	c.71-3086C>T		intron	N/A	ENSP00000327025.6
	RORC	ENST00000356728.11	TSL:1	c.8-3086C>T		intron	N/A	ENSP00000349164.6
	RORC	ENST00000652040.2		c.-129-3561C>T		intron	N/A	ENSP00000498548.2

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3333 AN: 152106 Hom.: 129 Cov.: 31

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0219 AC: 3335 AN: 152224 Hom.: 129 Cov.: 31 AF XY: 0.0211 AC XY: 1567 AN XY: 74434

African (AFR) AF: 0.0766 AC: 3177 AN: 41490

American (AMR) AF: 0.00719 AC: 110 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68036

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.00502 Hom.: 29

Bravo AF: 0.0251

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.77
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7546811; hg19: chr1-151792842;