rs7540530

Variant names:

• chr1-151818382-G-A
• rs7540530
• NM_005060.4:c.71-1102C>T

Variant summary

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

The NM_005060.4(RORC):​c.71-1102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,944 control chromosomes in the GnomAD database, including 15,096 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 (15096 hom., cov: 32)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 19 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.71-1102C>T		intron_variant	Intron 2 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.8-1102C>T		intron_variant	Intron 1 of 9		NP_001001523.1
RORC	XM_006711484.5	c.233-1102C>T		intron_variant	Intron 3 of 11		XP_006711547.3
RORC	XM_047427201.1	c.8-1102C>T		intron_variant	Intron 1 of 5		XP_047283157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7	c.71-1102C>T		intron_variant	Intron 2 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65984 AN: 151826 Hom.: 15094 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.434 AC: 66005 AN: 151944 Hom.: 15096 Cov.: 32 AF XY: 0.433 AC XY: 32164 AN XY: 74256

African (AFR) AF: 0.304 AC: 12593 AN: 41416

American (AMR) AF: 0.360 AC: 5498 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1367 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2327 AN: 5150

South Asian (SAS) AF: 0.432 AC: 2074 AN: 4798

European-Finnish (FIN) AF: 0.534 AC: 5645 AN: 10572

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35066 AN: 67946

Other (OTH) AF: 0.436 AC: 921 AN: 2112

Alfa AF: 0.488 Hom.: 78615

Bravo AF: 0.414

Asia WGS AF: 0.444 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.4
DANN	Benign	0.70
PhyloP100		-0.046
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: rs7540530; hg19: chr1-151790858;