chr1-151829880-T-A

Position:

• chr1-151829880-T-A

Variant summary

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

The NM_005060.4(RORC):​c.41-422A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 152,354 control chromosomes in the GnomAD database, including 465 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 0.073 (465 hom., cov: 32)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORC	NM_005060.4	c.41-422A>T		intron_variant		ENST00000318247.7	NP_005051.2
RORC	XM_006711484.5	c.203-422A>T		intron_variant			XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.41-422A>T		intron_variant		1	NM_005060.4	ENSP00000327025	P4

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11127 AN: 152236 Hom.: 466 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.0936

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

GnomAD4 genome AF: 0.0730 AC: 11125 AN: 152354 Hom.: 465 Cov.: 32 AF XY: 0.0723 AC XY: 5388 AN XY: 74516

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0857

Gnomad4 NFE AF: 0.0967

Gnomad4 OTH AF: 0.0940

Alfa AF: 0.0801 Hom.: 67

Bravo AF: 0.0700

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11801866; hg19: chr1-151802356;