chr1-151829545-C-T

Variant names:

• chr1-151829545-C-T
• rs6685811
• NM_005060.4:c.41-87G>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.41-87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,227,738 control chromosomes in the GnomAD database, including 251 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 0.025 (157 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (94 hom.)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• 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, 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 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.41-87G>A		intron	N/A	NP_005051.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	ENST00000318247.7	TSL:1 MANE Select	c.41-87G>A		intron	N/A	ENSP00000327025.6	P51449-1
	RORC	ENST00000859919.1		c.41-87G>A		intron	N/A	ENSP00000529978.1
	RORC	ENST00000859921.1		c.41-87G>A		intron	N/A	ENSP00000529980.1

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3716 AN: 152128 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00234 AC: 2516 AN: 1075492 Hom.: 94 AF XY: 0.00210 AC XY: 1117 AN XY: 530726

African (AFR) AF: 0.0900 AC: 1966 AN: 21850

American (AMR) AF: 0.00413 AC: 75 AN: 18150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16914

East Asian (EAS) AF: 0.00 AC: 0 AN: 30128

South Asian (SAS) AF: 0.000378 AC: 18 AN: 47600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48030

Middle Eastern (MID) AF: 0.00316 AC: 14 AN: 4430

European-Non Finnish (NFE) AF: 0.000208 AC: 175 AN: 843092

Other (OTH) AF: 0.00592 AC: 268 AN: 45298

GnomAD4 genome AF: 0.0245 AC: 3735 AN: 152246 Hom.: 157 Cov.: 32 AF XY: 0.0239 AC XY: 1778 AN XY: 74458

African (AFR) AF: 0.0859 AC: 3566 AN: 41506

American (AMR) AF: 0.00732 AC: 112 AN: 15304

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

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

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68016

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0207 Hom.: 11

Bravo AF: 0.0276

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.39
PhyloP100		1.4
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: rs6685811; hg19: chr1-151802021;