rs1805335

Variant names:

• chr9-107318737-A-G
• rs1805335
• NM_002874.5:c.554-15A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-107318737-A-G
• chr9-107318737-A-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.554-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,598,816 control chromosomes in the GnomAD database, including 239,997 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 0.55 (23467 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216530 hom.)
• Consequence: RAD23B NM_002874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 17 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 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.554-15A>G		intron	N/A	NP_002865.1	P54727-1
	RAD23B	NM_001244713.1		c.491-15A>G		intron	N/A	NP_001231642.1	B7Z4W4
	RAD23B	NM_001244724.2		c.338-15A>G		intron	N/A	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.554-15A>G		intron	N/A	ENSP00000350708.3	P54727-1
	RAD23B	ENST00000416373.6	TSL:1	c.338-15A>G		intron	N/A	ENSP00000405623.2	P54727-2
	RAD23B	ENST00000866019.1		c.554-15A>G		intron	N/A	ENSP00000536078.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84042 AN: 151760 Hom.: 23463 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.567

GnomAD2 exomes AF: 0.553 AC: 136508 AN: 246832 AF XY: 0.549

Gnomad AFR exome AF: 0.544

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.612

Gnomad EAS exome AF: 0.752

Gnomad FIN exome AF: 0.571

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.567

GnomAD4 exome AF: 0.545 AC: 788373 AN: 1446938 Hom.: 216530 Cov.: 33 AF XY: 0.542 AC XY: 389610 AN XY: 718938

African (AFR) AF: 0.550 AC: 18158 AN: 33006

American (AMR) AF: 0.516 AC: 22507 AN: 43600

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 15838 AN: 25848

East Asian (EAS) AF: 0.719 AC: 28363 AN: 39438

South Asian (SAS) AF: 0.468 AC: 39655 AN: 84812

European-Finnish (FIN) AF: 0.566 AC: 30132 AN: 53190

Middle Eastern (MID) AF: 0.602 AC: 3428 AN: 5696

European-Non Finnish (NFE) AF: 0.542 AC: 596639 AN: 1101572

Other (OTH) AF: 0.563 AC: 33653 AN: 59776

GnomAD4 genome AF: 0.554 AC: 84080 AN: 151878 Hom.: 23467 Cov.: 32 AF XY: 0.555 AC XY: 41150 AN XY: 74200

African (AFR) AF: 0.547 AC: 22631 AN: 41400

American (AMR) AF: 0.547 AC: 8351 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2154 AN: 3466

East Asian (EAS) AF: 0.753 AC: 3893 AN: 5172

South Asian (SAS) AF: 0.482 AC: 2323 AN: 4820

European-Finnish (FIN) AF: 0.574 AC: 6043 AN: 10524

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36845 AN: 67934

Other (OTH) AF: 0.569 AC: 1195 AN: 2100

Alfa AF: 0.536 Hom.: 12557

Bravo AF: 0.556

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1805335; hg19: chr9-110081018;