rs12030974

Variant names:

• chr1-151825819-G-A
• rs12030974
• NM_005060.4:c.70+3610C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151825819-G-A
• chr1-151825819-G-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.70+3610C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,299,052 control chromosomes in the GnomAD database, including 36,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3442 hom., cov: 32)
  • Exomes 𝑓: 0.23 (33496 hom.)
• Consequence: RORC NM_005060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.628
• Publications: 5 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=-0.77).
• BP6: Variant 1-151825819-G-A is Benign according to our data. Variant chr1-151825819-G-A is described in ClinVar as Benign. ClinVar VariationId is 2628168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005060.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	NM_005060.4	MANE Select	c.70+3610C>T		intron	N/A	NP_005051.2
	RORC	NM_001001523.2		c.7+111C>T		intron	N/A	NP_001001523.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	ENST00000318247.7	TSL:1 MANE Select	c.70+3610C>T		intron	N/A	ENSP00000327025.6
	RORC	ENST00000356728.11	TSL:1	c.7+111C>T		intron	N/A	ENSP00000349164.6
	RORC	ENST00000652040.2		c.-130+3610C>T		intron	N/A	ENSP00000498548.2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28000 AN: 151992 Hom.: 3440 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.227 AC: 260230 AN: 1146944 Hom.: 33496 AF XY: 0.234 AC XY: 134879 AN XY: 576902

African (AFR) AF: 0.0398 AC: 1080 AN: 27136

American (AMR) AF: 0.313 AC: 12944 AN: 41414

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 8425 AN: 22244

East Asian (EAS) AF: 0.421 AC: 15205 AN: 36146

South Asian (SAS) AF: 0.380 AC: 28161 AN: 74200

European-Finnish (FIN) AF: 0.143 AC: 7257 AN: 50700

Middle Eastern (MID) AF: 0.313 AC: 1593 AN: 5086

European-Non Finnish (NFE) AF: 0.207 AC: 174040 AN: 840364

Other (OTH) AF: 0.232 AC: 11525 AN: 49654

GnomAD4 genome AF: 0.184 AC: 27995 AN: 152108 Hom.: 3442 Cov.: 32 AF XY: 0.188 AC XY: 13990 AN XY: 74336

African (AFR) AF: 0.0455 AC: 1887 AN: 41518

American (AMR) AF: 0.251 AC: 3838 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2186 AN: 5150

South Asian (SAS) AF: 0.382 AC: 1837 AN: 4814

European-Finnish (FIN) AF: 0.150 AC: 1592 AN: 10600

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14574 AN: 67960

Other (OTH) AF: 0.216 AC: 456 AN: 2112

Alfa AF: 0.211 Hom.: 1349

Bravo AF: 0.187

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.3
DANN	Benign	0.67
PhyloP100		0.63
PromoterAI		0.21	Neutral
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: rs12030974; hg19: chr1-151798295; COSMIC: COSV59092111;