rs939595

Variant names:

• chr1-151811212-A-C
• rs939595
• NM_005060.4:c.1395+113T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-151811212-A-C
• chr1-151811212-A-G
• chr1-151811212-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005060.4(RORC):​c.1395+113T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 599,494 control chromosomes in the GnomAD database, including 124,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (31954 hom., cov: 31)
  • Exomes 𝑓: 0.64 (92911 hom.)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.91
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-151811212-A-C is Benign according to our data. Variant chr1-151811212-A-C is described in ClinVar as Benign. ClinVar VariationId is 2628210.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.1395+113T>G		intron_variant	Intron 10 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.1332+113T>G		intron_variant	Intron 9 of 9		NP_001001523.1
RORC	XM_006711484.5	c.1557+113T>G		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+113T>G		intron_variant	Intron 10 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97989 AN: 151876 Hom.: 31939 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.641 AC: 286769 AN: 447500 Hom.: 92911 AF XY: 0.644 AC XY: 151531 AN XY: 235252

African (AFR) AF: 0.685 AC: 9149 AN: 13352

American (AMR) AF: 0.606 AC: 12482 AN: 20614

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 6863 AN: 13124

East Asian (EAS) AF: 0.725 AC: 23501 AN: 32402

South Asian (SAS) AF: 0.747 AC: 29971 AN: 40124

European-Finnish (FIN) AF: 0.623 AC: 24498 AN: 39292

Middle Eastern (MID) AF: 0.544 AC: 1142 AN: 2100

European-Non Finnish (NFE) AF: 0.626 AC: 163604 AN: 261424

Other (OTH) AF: 0.621 AC: 15559 AN: 25068

GnomAD4 genome AF: 0.645 AC: 98045 AN: 151994 Hom.: 31954 Cov.: 31 AF XY: 0.645 AC XY: 47937 AN XY: 74276

African (AFR) AF: 0.690 AC: 28605 AN: 41448

American (AMR) AF: 0.584 AC: 8919 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3464

East Asian (EAS) AF: 0.737 AC: 3792 AN: 5146

South Asian (SAS) AF: 0.773 AC: 3720 AN: 4812

European-Finnish (FIN) AF: 0.619 AC: 6538 AN: 10558

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42698 AN: 67980

Other (OTH) AF: 0.616 AC: 1296 AN: 2104

Alfa AF: 0.626 Hom.: 80563

Bravo AF: 0.647

Asia WGS AF: 0.728 AC: 2533 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.011
DANN	Benign	0.32
PhyloP100		-2.9
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: rs939595; hg19: chr1-151783688; COSMIC: COSV59092154;