chr1-151809614-T-C

Variant names:

• chr1-151809614-T-C
• rs12045886
• NM_005060.4:c.1395+1711A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005060.4(RORC):​c.1395+1711A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,918 control chromosomes in the GnomAD database, including 6,470 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 0.29 (6470 hom., cov: 31)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.1395+1711A>G		intron_variant	Intron 10 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.1332+1711A>G		intron_variant	Intron 9 of 9		NP_001001523.1
RORC	XM_006711484.5	c.1557+1711A>G		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+1711A>G		intron_variant	Intron 10 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43555 AN: 151800 Hom.: 6473 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.287 AC: 43574 AN: 151918 Hom.: 6470 Cov.: 31 AF XY: 0.293 AC XY: 21743 AN XY: 74236

African (AFR) AF: 0.263 AC: 10909 AN: 41410

American (AMR) AF: 0.285 AC: 4355 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2425 AN: 5166

South Asian (SAS) AF: 0.423 AC: 2039 AN: 4820

European-Finnish (FIN) AF: 0.296 AC: 3128 AN: 10550

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18771 AN: 67926

Other (OTH) AF: 0.282 AC: 593 AN: 2106

Alfa AF: 0.283 Hom.: 10460

Bravo AF: 0.287

Asia WGS AF: 0.379 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.53
PhyloP100		-1.9
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: rs12045886; hg19: chr1-151782090;