dbSNP rs9826: RORC:c.*1049A>G (chr1-151806423-T-C) – 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.*1049A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 153,356 control chromosomes in the GnomAD database, including 7,758 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 0.30 ( 7684 hom., cov: 32)

Exomes 𝑓: 0.34 ( 74 hom. )

Consequence

RORC
NM_005060.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.481

Publications

30 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=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RORC	NM_005060.4 link	c.*1049A>G	3_prime_UTR_variant	Exon 11 of 11	ENST00000318247.7	NP_005051.2	P51449-1Q6I9R9
RORC	NM_001001523.2 link	c.*1049A>G	3_prime_UTR_variant	Exon 10 of 10		NP_001001523.1	P51449-2F1D8P6
RORC	XM_006711484.5 link	c.*1049A>G	3_prime_UTR_variant	Exon 12 of 12		XP_006711547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORC	ENST00000318247.7 link	c.*1049A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_005060.4	ENSP00000327025.6		P51449-1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45627

AN:

152082

Hom.:

7673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.345

GnomAD4 exome

AF:

0.342

AC:

395

AN:

1154

Hom.:

Cov.:

AF XY:

0.343

AC XY:

201

AN XY:

586

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.335

AC:

362

AN:

1082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.440

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.300

AC:

45668

AN:

152202

Hom.:

7684

Cov.:

AF XY:

0.304

AC XY:

22586

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.158

AC:

6547

AN:

41548

American (AMR)

AF:

0.396

AC:

6057

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1735

AN:

3472

East Asian (EAS)

AF:

0.303

AC:

1563

AN:

5166

South Asian (SAS)

AF:

0.261

AC:

1255

AN:

4814

European-Finnish (FIN)

AF:

0.361

AC:

3829

AN:

10594

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23586

AN:

67988

Other (OTH)

AF:

0.348

AC:

736

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1600

3199

4799

6398

7998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.343

Hom.:

15700

Bravo

AF:

0.293

Asia WGS

AF:

0.280

AC:

975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.5

(source)

DANN

Benign

0.54

PhyloP100

-0.48

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over