dbSNP rs1521186: RORC:c.1286-637C>T (chr1-151812071-G-A) – 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.1286-637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,950 control chromosomes in the GnomAD database, including 14,259 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 0.43 ( 14258 hom., cov: 31)

Exomes 𝑓: 0.38 ( 1 hom. )

Consequence

RORC
NM_005060.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.178

Publications

10 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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4 link	c.1286-637C>T	intron_variant	Intron 9 of 10	ENST00000318247.7	NP_005051.2	P51449-1Q6I9R9
RORC	NM_001001523.2 link	c.1223-637C>T	intron_variant	Intron 8 of 9		NP_001001523.1	P51449-2F1D8P6
RORC	XM_006711484.5 link	c.1448-637C>T	intron_variant	Intron 10 of 11		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7 link	c.1286-637C>T		intron_variant	Intron 9 of 10	1	NM_005060.4	ENSP00000327025.6		P51449-1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65312

AN:

151816

Hom.:

14266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

Cov.:

AF XY:

0.400

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.357

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.430

AC:

65325

AN:

151934

Hom.:

14258

Cov.:

AF XY:

0.430

AC XY:

31904

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.391

AC:

16198

AN:

41428

American (AMR)

AF:

0.407

AC:

6209

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1385

AN:

3470

East Asian (EAS)

AF:

0.505

AC:

2602

AN:

5148

South Asian (SAS)

AF:

0.652

AC:

3136

AN:

4812

European-Finnish (FIN)

AF:

0.372

AC:

3927

AN:

10552

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.449

AC:

30507

AN:

67940

Other (OTH)

AF:

0.436

AC:

922

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1906

3813

5719

7626

9532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.433

Hom.:

19955

Bravo

AF:

0.430

Asia WGS

AF:

0.530

AC:

1844

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.6

(source)

DANN

Benign

0.69

PhyloP100

0.18

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

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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