chr1-151829880-T-A

Variant names:

• chr1-151829880-T-A
• rs11801866
• NM_005060.4:c.41-422A>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.41-422A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 152,354 control chromosomes in the GnomAD database, including 465 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 0.073 (465 hom., cov: 32)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.0947 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.41-422A>T		intron	N/A	NP_005051.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	ENST00000318247.7	TSL:1 MANE Select	c.41-422A>T		intron	N/A	ENSP00000327025.6
	RORC	ENST00000652040.2		c.-159-422A>T		intron	N/A	ENSP00000498548.2
	RORC	ENST00000638901.1	TSL:2	n.*78-422A>T		intron	N/A	ENSP00000492395.1

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11127 AN: 152236 Hom.: 466 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.0936

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

GnomAD4 genome AF: 0.0730 AC: 11125 AN: 152354 Hom.: 465 Cov.: 32 AF XY: 0.0723 AC XY: 5388 AN XY: 74516

African (AFR) AF: 0.0407 AC: 1693 AN: 41580

American (AMR) AF: 0.0674 AC: 1032 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0530 AC: 256 AN: 4832

European-Finnish (FIN) AF: 0.0857 AC: 911 AN: 10624

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0967 AC: 6577 AN: 68028

Other (OTH) AF: 0.0940 AC: 199 AN: 2116

Alfa AF: 0.0801 Hom.: 67

Bravo AF: 0.0700

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.53
PhyloP100		-0.027
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: rs11801866; hg19: chr1-151802356;