rs1805329

Variant names:

• chr9-107322047-C-T
• rs1805329
• NM_002874.5:c.746C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002874.5(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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2366 hom., cov: 33)
  • Exomes 𝑓: 0.20 (29456 hom.)
• Consequence: RAD23B NM_002874.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• Publications: 83 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002874.5. 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
	RAD23B	NM_002874.5	MANE Select	c.746C>T	p.Ala249Val	missense	Exon 7 of 10	NP_002865.1	P54727-1
	RAD23B	NM_001244713.1		c.683C>T	p.Ala228Val	missense	Exon 7 of 10	NP_001231642.1	B7Z4W4
	RAD23B	NM_001244724.2		c.530C>T	p.Ala177Val	missense	Exon 7 of 10	NP_001231653.1	P54727-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD23B	ENST00000358015.8	TSL:1 MANE Select	c.746C>T	p.Ala249Val	missense	Exon 7 of 10	ENSP00000350708.3	P54727-1
	RAD23B	ENST00000416373.6	TSL:1	c.530C>T	p.Ala177Val	missense	Exon 7 of 10	ENSP00000405623.2	P54727-2
	RAD23B	ENST00000866019.1		c.746C>T	p.Ala249Val	missense	Exon 7 of 10	ENSP00000536078.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23931 AN: 152048 Hom.: 2366 Cov.: 33

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

GnomAD2 exomes AF: 0.199 AC: 49753 AN: 249664 AF XY: 0.196

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 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.: 32 AF XY: 0.195 AC XY: 141582 AN XY: 726090

African (AFR) AF: 0.0299 AC: 1001 AN: 33438

American (AMR) AF: 0.309 AC: 13715 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 2353 AN: 26104

East Asian (EAS) AF: 0.185 AC: 7317 AN: 39556

South Asian (SAS) AF: 0.193 AC: 16545 AN: 85882

European-Finnish (FIN) AF: 0.245 AC: 13093 AN: 53364

Middle Eastern (MID) AF: 0.111 AC: 640 AN: 5764

European-Non Finnish (NFE) AF: 0.198 AC: 219714 AN: 1110874

Other (OTH) AF: 0.176 AC: 10606 AN: 60304

GnomAD4 genome AF: 0.157 AC: 23933 AN: 152164 Hom.: 2366 Cov.: 33 AF XY: 0.161 AC XY: 11963 AN XY: 74380

African (AFR) AF: 0.0385 AC: 1597 AN: 41530

American (AMR) AF: 0.231 AC: 3526 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.185 AC: 958 AN: 5172

South Asian (SAS) AF: 0.179 AC: 865 AN: 4822

European-Finnish (FIN) AF: 0.247 AC: 2611 AN: 10574

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.200 AC: 13630 AN: 67990

Other (OTH) AF: 0.133 AC: 281 AN: 2114

Alfa AF: 0.173 Hom.: 1224

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.095
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.061
Sift	Benign	0.23	T
Sift4G	Benign	0.27	T
Polyphen		0.30	B
Vest4		0.037
MPC		0.50
ClinPred		0.023	T
GERP RS		5.3
Varity_R		0.076
gMVP		0.35
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1805329; hg19: chr9-110084328; COSMIC: COSV63657702;