rs3828057

Variant names:

• chr1-151807701-C-T
• rs3828057
• NM_005060.4:c.1396-68G>A

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.1396-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,539,496 control chromosomes in the GnomAD database, including 140,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10796 hom., cov: 32)
  • Exomes 𝑓: 0.43 (129303 hom.)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.458
• Publications: 27 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=-0.83).
• BP6: Variant 1-151807701-C-T is Benign according to our data. Variant chr1-151807701-C-T is described in ClinVar as Benign. ClinVar VariationId is 2628172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4	c.1396-68G>A		intron_variant	Intron 10 of 10	ENST00000318247.7	NP_005051.2
RORC	NM_001001523.2	c.1333-68G>A		intron_variant	Intron 9 of 9		NP_001001523.1
RORC	XM_006711484.5	c.1558-68G>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.1396-68G>A		intron_variant	Intron 10 of 10	1	NM_005060.4	ENSP00000327025.6

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54952 AN: 151992 Hom.: 10796 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.425 AC: 590296 AN: 1387388 Hom.: 129303 AF XY: 0.425 AC XY: 292460 AN XY: 688468

African (AFR) AF: 0.245 AC: 7788 AN: 31770

American (AMR) AF: 0.237 AC: 9842 AN: 41524

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 7492 AN: 23510

East Asian (EAS) AF: 0.232 AC: 9071 AN: 39072

South Asian (SAS) AF: 0.373 AC: 29817 AN: 79988

European-Finnish (FIN) AF: 0.424 AC: 21060 AN: 49720

Middle Eastern (MID) AF: 0.301 AC: 1638 AN: 5444

European-Non Finnish (NFE) AF: 0.455 AC: 481335 AN: 1058788

Other (OTH) AF: 0.387 AC: 22253 AN: 57572

GnomAD4 genome AF: 0.361 AC: 54955 AN: 152108 Hom.: 10796 Cov.: 32 AF XY: 0.354 AC XY: 26344 AN XY: 74366

African (AFR) AF: 0.252 AC: 10442 AN: 41494

American (AMR) AF: 0.274 AC: 4190 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1050 AN: 5176

South Asian (SAS) AF: 0.374 AC: 1801 AN: 4814

European-Finnish (FIN) AF: 0.409 AC: 4328 AN: 10576

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30848 AN: 67970

Other (OTH) AF: 0.352 AC: 744 AN: 2114

Alfa AF: 0.425 Hom.: 8007

Bravo AF: 0.346

Asia WGS AF: 0.308 AC: 1073 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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.28
PhyloP100		-0.46
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: rs3828057; hg19: chr1-151780177; COSMIC: COSV59092182; COSMIC: COSV59092182;