9-107306603-G-A

Variant names:

• chr9-107306603-G-A
• rs146029019
• NM_002874.5:c.453G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_002874.5(RAD23B):​c.453G>A​(p.Lys151Lys) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (13 hom.)
• Consequence: RAD23B NM_002874.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0160

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

Verdict is Benign. Variant got -8 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
RAD23B	NM_002874.5	c.453G>A	p.Lys151Lys	synonymous_variant	Exon 4 of 10	ENST00000358015.8	NP_002865.1
RAD23B	NM_001244713.1	c.390G>A	p.Lys130Lys	synonymous_variant	Exon 4 of 10		NP_001231642.1
RAD23B	NM_001244724.2	c.237G>A	p.Lys79Lys	synonymous_variant	Exon 4 of 10		NP_001231653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8	c.453G>A	p.Lys151Lys	synonymous_variant	Exon 4 of 10	1	NM_002874.5	ENSP00000350708.3
RAD23B	ENST00000416373.6	c.237G>A	p.Lys79Lys	synonymous_variant	Exon 4 of 10	1		ENSP00000405623.2
RAD23B	ENST00000457811.1	c.60G>A	p.Lys20Lys	synonymous_variant	Exon 1 of 4	3		ENSP00000396975.1
RAD23B	ENST00000419616.5	c.*13G>A		downstream_gene_variant		3		ENSP00000416868.1

Frequencies

GnomAD3 genomes AF: 0.00267 AC: 407 AN: 152176 Hom.: 2 Cov.: 31

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.: 2 AF XY: 0.00301 AC XY: 409 AN XY: 135814

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.: 13 Cov.: 31 AF XY: 0.00381 AC XY: 2770 AN XY: 727240

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.: 2 Cov.: 31 AF XY: 0.00243 AC XY: 181 AN XY: 74466

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.: 0

Bravo AF: 0.00283

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RAD23B-related disorder Benign:1

Apr 08, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	12
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

Other links and lift over

dbSNP: rs146029019; hg19: chr9-110068884; COSMIC: COSV63658729; COSMIC: COSV63658729;