Genetic Variant RORC:c.41-87G>A (chr1-151829545-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.41-87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,227,738 control chromosomes in the GnomAD database, including 251 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 0.025 ( 157 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 94 hom. )

Consequence

RORC
NM_005060.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

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

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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4 link	c.41-87G>A		intron_variant	Intron 1 of 10	ENST00000318247.7	NP_005051.2	P51449-1Q6I9R9
RORC	XM_006711484.5 link	c.203-87G>A		intron_variant	Intron 2 of 11		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7 link	c.41-87G>A		intron_variant	Intron 1 of 10	1	NM_005060.4	ENSP00000327025.6		P51449-1

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3716

AN:

152128

Hom.:

156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0857

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0143

GnomAD4 exome

AF:

0.00234

AC:

2516

AN:

1075492

Hom.:

AF XY:

0.00210

AC XY:

1117

AN XY:

530726

show subpopulations

African (AFR)

AF:

0.0900

AC:

1966

AN:

21850

American (AMR)

AF:

0.00413

AC:

AN:

18150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16914

East Asian (EAS)

AF:

0.00

AC:

AN:

30128

South Asian (SAS)

AF:

0.000378

AC:

AN:

47600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48030

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

4430

European-Non Finnish (NFE)

AF:

0.000208

AC:

175

AN:

843092

Other (OTH)

AF:

0.00592

AC:

268

AN:

45298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

115

230

344

459

574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0245

AC:

3735

AN:

152246

Hom.:

157

Cov.:

AF XY:

0.0239

AC XY:

1778

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0859

AC:

3566

AN:

41506

American (AMR)

AF:

0.00732

AC:

112

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68016

Other (OTH)

AF:

0.0142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

161

322

482

643

804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0207

Hom.:

Bravo

AF:

0.0276

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.9

(source)

DANN

Benign

0.39

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over