rs11573709

Variant names:

• chr9-107322974-G-A
• rs11573709
• NM_002874.5:c.817+856G>A

Variant summary

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

The NM_002874.5(RAD23B):​c.817+856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,986 control chromosomes in the GnomAD database, including 5,595 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.

• Frequency: Genomes: 𝑓 0.25 (5595 hom., cov: 32)
• Consequence: RAD23B NM_002874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 11 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD23B	NM_002874.5	MANE Select	c.817+856G>A		intron	N/A	NP_002865.1
	RAD23B	NM_001244713.1		c.754+856G>A		intron	N/A	NP_001231642.1
	RAD23B	NM_001244724.2		c.601+856G>A		intron	N/A	NP_001231653.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD23B	ENST00000358015.8	TSL:1 MANE Select	c.817+856G>A		intron	N/A	ENSP00000350708.3
	RAD23B	ENST00000416373.6	TSL:1	c.601+856G>A		intron	N/A	ENSP00000405623.2
	RAD23B	ENST00000866019.1		c.817+856G>A		intron	N/A	ENSP00000536078.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38500 AN: 151866 Hom.: 5567 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38583 AN: 151986 Hom.: 5595 Cov.: 32 AF XY: 0.251 AC XY: 18619 AN XY: 74262

African (AFR) AF: 0.386 AC: 16014 AN: 41434

American (AMR) AF: 0.183 AC: 2793 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3464

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5178

South Asian (SAS) AF: 0.286 AC: 1379 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1632 AN: 10530

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14862 AN: 67964

Other (OTH) AF: 0.259 AC: 548 AN: 2112

Alfa AF: 0.233 Hom.: 8729

Bravo AF: 0.259

Asia WGS AF: 0.155 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.42
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs11573709; hg19: chr9-110085255;