NM_002874.5:c.453G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.039).
• 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 VariationId 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.

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.453G>A	p.Lys151Lys	synonymous	Exon 4 of 10	NP_002865.1	P54727-1
	RAD23B	NM_001244713.1		c.390G>A	p.Lys130Lys	synonymous	Exon 4 of 10	NP_001231642.1	B7Z4W4
	RAD23B	NM_001244724.2		c.237G>A	p.Lys79Lys	synonymous	Exon 4 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.453G>A	p.Lys151Lys	synonymous	Exon 4 of 10	ENSP00000350708.3	P54727-1
	RAD23B	ENST00000416373.6	TSL:1	c.237G>A	p.Lys79Lys	synonymous	Exon 4 of 10	ENSP00000405623.2	P54727-2
	RAD23B	ENST00000866019.1		c.453G>A	p.Lys151Lys	synonymous	Exon 4 of 10	ENSP00000536078.1

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

GnomAD2 exomes AF: 0.00291 AC: 731 AN: 251218 AF XY: 0.00301

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 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

African (AFR) AF: 0.000508 AC: 17 AN: 33480

American (AMR) AF: 0.00217 AC: 97 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00241 AC: 63 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00197 AC: 170 AN: 86258

European-Finnish (FIN) AF: 0.000655 AC: 35 AN: 53420

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5768

European-Non Finnish (NFE) AF: 0.00446 AC: 4956 AN: 1111994

Other (OTH) AF: 0.00374 AC: 226 AN: 60396

GnomAD4 genome AF: 0.00267 AC: 407 AN: 152294 Hom.: 2 Cov.: 31 AF XY: 0.00243 AC XY: 181 AN XY: 74466

African (AFR) AF: 0.000625 AC: 26 AN: 41570

American (AMR) AF: 0.00203 AC: 31 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00476 AC: 324 AN: 68028

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

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

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RAD23B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.016
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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