Variant 9-107322047-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000358015.8(RAD23B):c.746C>T(p.Ala249Val) variant causes a missense change. The variant allele was found at a frequency of 0.192 in 1,611,794 control chromosomes in the GnomAD database, including 31,822 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2366 hom., cov: 33)

Exomes 𝑓: 0.20 ( 29456 hom. )

Consequence

RAD23B
ENST00000358015.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.80

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034525692).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAD23B	NM_002874.5 linkuse as main transcript	c.746C>T	p.Ala249Val	missense_variant	7/10	ENST00000358015.8	NP_002865.1
RAD23B	NM_001244713.1 linkuse as main transcript	c.683C>T	p.Ala228Val	missense_variant	7/10		NP_001231642.1
RAD23B	NM_001244724.2 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	7/10		NP_001231653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8 linkuse as main transcript	c.746C>T	p.Ala249Val	missense_variant	7/10	1	NM_002874.5	ENSP00000350708	P1	P54727-1
RAD23B	ENST00000416373.6 linkuse as main transcript	c.530C>T	p.Ala177Val	missense_variant	7/10	1		ENSP00000405623		P54727-2
RAD23B	ENST00000457811.1 linkuse as main transcript	c.290+3168C>T		intron_variant		3		ENSP00000396975

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23931

AN:

152048

Hom.:

2366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.0931

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.199

AC:

49753

AN:

249664

Hom.:

5693

AF XY:

0.196

AC XY:

26439

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.0886

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.248

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.195

AC:

284984

AN:

1459630

Hom.:

29456

Cov.:

AF XY:

0.195

AC XY:

141582

AN XY:

726090

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.0901

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.198

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.157

AC:

23933

AN:

152164

Hom.:

2366

Cov.:

AF XY:

0.161

AC XY:

11963

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.0931

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.175

Hom.:

1223

Bravo

AF:

0.151

TwinsUK

AF:

0.186

AC:

691

ALSPAC

AF:

0.189

AC:

727

ESP6500AA

AF:

0.0490

AC:

216

ESP6500EA

AF:

0.183

AC:

1577

ExAC

AF:

0.195

AC:

23681

Asia WGS

AF:

0.171

AC:

595

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.

Eigen

Benign

-0.095

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.94

P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.061

Sift

Benign

0.23

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.30

B;.

Vest4

0.037

MPC

0.50

ClinPred

0.023

GERP RS

5.3

Varity_R

0.076

gMVP

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over