dbSNP rs9017: RORC:c.*1265G>A (chr1-151806207-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005060.4(RORC):c.*1265G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,836 control chromosomes in the GnomAD database, including 27,390 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 27153 hom., cov: 30)

Exomes 𝑓: 0.66 ( 237 hom. )

Consequence

RORC
NM_005060.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Publications

22 publications found

Variant links:

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, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

RORC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORC	NM_005060.4	MANE Select	c.*1265G>A		3_prime_UTR	Exon 11 of 11	NP_005051.2
	RORC	NM_001001523.2		c.*1265G>A		3_prime_UTR	Exon 10 of 10	NP_001001523.1	P51449-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RORC	ENST00000318247.7	TSL:1 MANE Select	c.*1265G>A	3_prime_UTR	Exon 11 of 11	ENSP00000327025.6	P51449-1
RORC	ENST00000356728.11	TSL:1	c.*1265G>A	3_prime_UTR	Exon 10 of 10	ENSP00000349164.6	P51449-2
RORC	ENST00000859919.1		c.*1265G>A	3_prime_UTR	Exon 11 of 11	ENSP00000529978.1

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89722

AN:

151648

Hom.:

27148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.749

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.565

GnomAD4 exome

AF:

0.658

AC:

705

AN:

1072

Hom.:

237

Cov.:

AF XY:

0.660

AC XY:

355

AN XY:

538

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.662

AC:

690

AN:

1042

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.591

AC:

89760

AN:

151764

Hom.:

27153

Cov.:

AF XY:

0.582

AC XY:

43193

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.579

AC:

23948

AN:

41354

American (AMR)

AF:

0.472

AC:

7205

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1726

AN:

3472

East Asian (EAS)

AF:

0.328

AC:

1687

AN:

5142

South Asian (SAS)

AF:

0.496

AC:

2385

AN:

4804

European-Finnish (FIN)

AF:

0.638

AC:

6688

AN:

10486

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.649

AC:

44107

AN:

67928

Other (OTH)

AF:

0.563

AC:

1186

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1780

3559

5339

7118

8898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.612

Hom.:

36577

Bravo

AF:

0.580

Asia WGS

AF:

0.478

AC:

1661

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over