1-151809858-C-G

Position:

• chr1-151809858-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RORC	NM_005060.4	c.1395+1467G>C		intron_variant		ENST00000318247.7
RORC	NM_001001523.2	c.1332+1467G>C		intron_variant
RORC	XM_006711484.5	c.1557+1467G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7	c.1395+1467G>C		intron_variant		1	NM_005060.4	P4

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

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.267

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10494269; hg19: chr1-151782334;