Variant 9-107306603-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002874.5(RAD23B):c.453G>A(p.Lys151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,614,170 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 13 hom. )

Consequence

RAD23B
NM_002874.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0160

Variant links:

Genes affected

RAD23B (HGNC:9813): (RAD23 homolog B, nucleotide excision repair protein) The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in the nucleotide excision repair (NER). This protein was found to be a component of the protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-c) cell extracts in vitro. This protein was also shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, and thus this protein may be involved in the ubiquitin mediated proteolytic pathway in cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2011]

RAD23B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 9-107306603-G-A is Benign according to our data. Variant chr9-107306603-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050247.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.016 with no splicing effect.

BS2

High AC in GnomAd4 at 407 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RAD23B	NM_002874.5 linkuse as main transcript	c.453G>A	p.Lys151=	synonymous_variant	4/10	ENST00000358015.8
RAD23B	NM_001244713.1 linkuse as main transcript	c.390G>A	p.Lys130=	synonymous_variant	4/10
RAD23B	NM_001244724.2 linkuse as main transcript	c.237G>A	p.Lys79=	synonymous_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD23B	ENST00000358015.8 linkuse as main transcript	c.453G>A	p.Lys151=	synonymous_variant	4/10	1	NM_002874.5	P1	P54727-1
RAD23B	ENST00000416373.6 linkuse as main transcript	c.237G>A	p.Lys79=	synonymous_variant	4/10	1			P54727-2
RAD23B	ENST00000457811.1 linkuse as main transcript	c.63G>A	p.Lys21=	synonymous_variant	1/4	3
RAD23B	ENST00000419616.5 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

407

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00476

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00291

AC:

731

AN:

251218

Hom.:

AF XY:

0.00301

AC XY:

409

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00473

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00382

AC:

5585

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2770

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00446

Gnomad4 OTH exome

AF:

0.00374

GnomAD4 genome

AF:

0.00267

AC:

407

AN:

152294

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00476

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00362

Hom.:

Bravo

AF:

0.00283

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RAD23B-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 08, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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