chr1-151829204-G-A

Variant names:

• chr1-151829204-G-A
• rs4845604
• NM_005060.4:c.70+225C>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.70+225C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 149,112 control chromosomes in the GnomAD database, including 2,369 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 0.17 (2369 hom., cov: 29)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 59 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.70+225C>T		intron_variant	Intron 2 of 10	ENST00000318247.7	NP_005051.2
RORC	XM_006711484.5	c.232+225C>T		intron_variant	Intron 3 of 11		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.70+225C>T		intron_variant	Intron 2 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25071 AN: 149002 Hom.: 2362 Cov.: 29

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.168 AC: 25100 AN: 149112 Hom.: 2369 Cov.: 29 AF XY: 0.166 AC XY: 12004 AN XY: 72492

African (AFR) AF: 0.261 AC: 10534 AN: 40416

American (AMR) AF: 0.131 AC: 1936 AN: 14734

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3456

East Asian (EAS) AF: 0.0290 AC: 145 AN: 5006

South Asian (SAS) AF: 0.0945 AC: 448 AN: 4740

European-Finnish (FIN) AF: 0.113 AC: 1119 AN: 9898

Middle Eastern (MID) AF: 0.131 AC: 38 AN: 290

European-Non Finnish (NFE) AF: 0.146 AC: 9857 AN: 67602

Other (OTH) AF: 0.174 AC: 359 AN: 2062

Alfa AF: 0.147 Hom.: 4789

Bravo AF: 0.172

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.52
DANN	Benign	0.46
PhyloP100		-0.53
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: rs4845604; hg19: chr1-151801680;