NM_005060.4:c.1395+1467G>C

Variant names:

• chr1-151809858-C-G
• rs10494269
• NM_005060.4:c.1395+1467G>C

Variant summary

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

The NM_005060.4(RORC):​c.1395+1467G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,136 control chromosomes in the GnomAD database, including 4,241 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 0.22 (4241 hom., cov: 32)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 11 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=-0.31).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.1395+1467G>C		intron_variant	Intron 10 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.1332+1467G>C		intron_variant	Intron 9 of 9		NP_001001523.1
RORC	XM_006711484.5	c.1557+1467G>C		intron_variant	Intron 11 of 11		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.1395+1467G>C		intron_variant	Intron 10 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34158 AN: 152018 Hom.: 4227 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.225 AC: 34201 AN: 152136 Hom.: 4241 Cov.: 32 AF XY: 0.229 AC XY: 17021 AN XY: 74364

African (AFR) AF: 0.163 AC: 6774 AN: 41496

American (AMR) AF: 0.350 AC: 5349 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1453 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1300 AN: 5166

South Asian (SAS) AF: 0.181 AC: 870 AN: 4816

European-Finnish (FIN) AF: 0.261 AC: 2762 AN: 10578

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14895 AN: 68008

Other (OTH) AF: 0.267 AC: 565 AN: 2116

Alfa AF: 0.0787 Hom.: 118

Bravo AF: 0.225

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		1.0
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: rs10494269; hg19: chr1-151782334;