chr1-151812071-G-A

Position:

• chr1-151812071-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000318247.7(RORC):​c.1286-637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,950 control chromosomes in the GnomAD database, including 14,259 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 0.43 (14258 hom., cov: 31)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: RORC ENST00000318247.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORC	NM_005060.4	c.1286-637C>T		intron_variant		ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.1223-637C>T		intron_variant			NP_001001523.1
RORC	XM_006711484.5	c.1448-637C>T		intron_variant			XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.1286-637C>T		intron_variant		1	NM_005060.4	ENSP00000327025	P4

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65312 AN: 151816 Hom.: 14266 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.375 AC: 6 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.430 AC: 65325 AN: 151934 Hom.: 14258 Cov.: 31 AF XY: 0.430 AC XY: 31904 AN XY: 74252

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.436

Alfa AF: 0.380 Hom.: 1980

Bravo AF: 0.430

Asia WGS AF: 0.530 AC: 1844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.69

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: rs1521186; hg19: chr1-151784547;