1-151807623-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005060.4(RORC):c.1406A>G(p.Lys469Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,614,110 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K469N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0048 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 58 hom. )

Consequence

RORC
NM_005060.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.67

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004697144).

BP6

Variant 1-151807623-T-C is Benign according to our data. Variant chr1-151807623-T-C is described in ClinVar as [Benign]. Clinvar id is 712886.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-151807623-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RORC	NM_005060.4 linkuse as main transcript	c.1406A>G	p.Lys469Arg	missense_variant	11/11	ENST00000318247.7
RORC	NM_001001523.2 linkuse as main transcript	c.1343A>G	p.Lys448Arg	missense_variant	10/10
RORC	XM_006711484.5 linkuse as main transcript	c.1568A>G	p.Lys523Arg	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORC	ENST00000318247.7 linkuse as main transcript	c.1406A>G	p.Lys469Arg	missense_variant	11/11	1	NM_005060.4	P4	P51449-1

Frequencies

GnomAD3 genomes

AF:

0.00483

AC:

735

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0585

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00564

AC:

1416

AN:

251014

Hom.:

AF XY:

0.00585

AC XY:

794

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0558

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00240

AC:

3509

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1745

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0496

Gnomad4 NFE exome

AF:

0.000678

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00483

AC:

735

AN:

152306

Hom.:

Cov.:

AF XY:

0.00742

AC XY:

553

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0585

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000533

ExAC

AF:

0.00462

AC:

561

EpiCase

AF:

0.000491

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.080

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.026

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Uncertain

-0.032

MutationTaster

Benign

0.87

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.90

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.14

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.53

.;P

Vest4

0.39

MVP

0.36

MPC

0.45

ClinPred

0.023

GERP RS

5.4

Varity_R

0.22

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over