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. Variant got -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

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 -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 id 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

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.747

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.621

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

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.616

Alfa AF: 0.618 Hom.: 46304

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

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: rs939595; hg19: chr1-151783688; COSMIC: COSV59092154;