1-151809654-G-T

Variant names:

• chr1-151809654-G-T
• rs1521177
• NM_005060.4:c.1395+1671C>A

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+1671C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,880 control chromosomes in the GnomAD database, including 26,443 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 0.58 (26443 hom., cov: 30)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 17 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.1395+1671C>A		intron_variant	Intron 10 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.1332+1671C>A		intron_variant	Intron 9 of 9		NP_001001523.1
RORC	XM_006711484.5	c.1557+1671C>A		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+1671C>A		intron_variant	Intron 10 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88459 AN: 151762 Hom.: 26422 Cov.: 30

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.583 AC: 88528 AN: 151880 Hom.: 26443 Cov.: 30 AF XY: 0.585 AC XY: 43445 AN XY: 74220

African (AFR) AF: 0.675 AC: 27928 AN: 41380

American (AMR) AF: 0.516 AC: 7886 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3683 AN: 5158

South Asian (SAS) AF: 0.708 AC: 3410 AN: 4818

European-Finnish (FIN) AF: 0.578 AC: 6101 AN: 10554

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36267 AN: 67912

Other (OTH) AF: 0.550 AC: 1160 AN: 2110

Alfa AF: 0.541 Hom.: 37191

Bravo AF: 0.584

Asia WGS AF: 0.701 AC: 2436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.27
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: rs1521177; hg19: chr1-151782130;