Genetic Variant RORB:c.7+20C>A (chr9-74498003-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006914.4(RORB):c.7+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,607,336 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

RORB
NM_006914.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.210

Publications

0 publications found

Variant links:

Genes affected

RORB (HGNC:10259): (RAR related orphan receptor B) The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It is a DNA-binding protein that can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, and to help regulate the expression of some genes involved in circadian rhythm. [provided by RefSeq, Feb 2014]

RORB links:

RORB-AS1 (HGNC:49803): (RORB antisense RNA 1)

RORB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-74498003-C-A is Benign according to our data. Variant chr9-74498003-C-A is described in ClinVar as Benign. ClinVar VariationId is 1528222.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 431 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006914.4. 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
	RORB	NM_006914.4	MANE Select	c.7+20C>A		intron	N/A	NP_008845.2
	RORB-AS1	NR_125791.1		n.312+239G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RORB	ENST00000376896.8	TSL:1 MANE Select	c.7+20C>A	intron	N/A	ENSP00000366093.2	Q92753-1
RORB-AS1	ENST00000417576.2	TSL:5	n.886+239G>T	intron	N/A
RORB-AS1	ENST00000773819.1		n.124+239G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

431

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000805

AC:

192

AN:

238444

AF XY:

0.000616

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.000502

Gnomad ASJ exome

AF:

0.000508

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000277

Gnomad OTH exome

AF:

0.000854

GnomAD4 exome

AF:

0.000315

AC:

458

AN:

1455144

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

188

AN XY:

723778

show subpopulations

African (AFR)

AF:

0.0102

AC:

341

AN:

33458

American (AMR)

AF:

0.000518

AC:

AN:

44368

Ashkenazi Jewish (ASJ)

AF:

0.000691

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.00

AC:

AN:

85682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49202

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1110806

Other (OTH)

AF:

0.00110

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00283

AC:

431

AN:

152192

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

208

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00978

AC:

406

AN:

41530

American (AMR)

AF:

0.00131

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000178

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over