rs34830957

chr1-151816776-G-Achr1-151816776-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_005060.4(RORC):c.186C>T(p.Asn62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,566,068 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (38 hom.)
• Consequence: RORC NM_005060.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.406

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-151816776-G-A is Benign according to our data. Variant chr1-151816776-G-A is described in ClinVar as [Benign]. Clinvar id is 475711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.406 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2056/152326) while in subpopulation AFR AF= 0.0476 (1978/41576). AF 95% confidence interval is 0.0458. There are 47 homozygotes in gnomad4. There are 987 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORC	NM_005060.4	c.186C>T	p.Asn62=	synonymous_variant	4/11	ENST00000318247.7
RORC	NM_001001523.2	c.123C>T	p.Asn41=	synonymous_variant	3/10
RORC	XM_006711484.5	c.348C>T	p.Asn116=	synonymous_variant	5/12
RORC	XM_047427201.1	c.123C>T	p.Asn41=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7	c.186C>T	p.Asn62=	synonymous_variant	4/11	1	NM_005060.4	P4

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2053 AN: 152208 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00351 AC: 744 AN: 211900 Hom.: 20 AF XY: 0.00246 AC XY: 280 AN XY: 113908

Gnomad AFR exome AF: 0.0471

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000601

Gnomad SAS exome AF: 0.0000845

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.00129 AC: 1823 AN: 1413742 Hom.: 38 Cov.: 31 AF XY: 0.00110 AC XY: 768 AN XY: 696964

Gnomad4 AFR exome AF: 0.0466

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000563

Gnomad4 OTH exome AF: 0.00289

GnomAD4 genome AF: 0.0135 AC: 2056 AN: 152326 Hom.: 47 Cov.: 33 AF XY: 0.0133 AC XY: 987 AN XY: 74480

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00465 Hom.: 8

Bravo AF: 0.0150

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	11
Dann	Benign	0.68

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: rs34830957; hg19: chr1-151789252;