rs1805335

chr9-107318737-A-Gchr9-107318737-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002874.5(RAD23B):c.554-15A>G variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD23B	NM_002874.5	c.554-15A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000358015.8
RAD23B	NM_001244713.1	c.491-15A>G		splice_polypyrimidine_tract_variant, intron_variant
RAD23B	NM_001244724.2	c.338-15A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD23B	ENST00000358015.8	c.554-15A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002874.5	P1
RAD23B	ENST00000416373.6	c.338-15A>G		splice_polypyrimidine_tract_variant, intron_variant		1
RAD23B	ENST00000457811.1	c.163-15A>G		splice_polypyrimidine_tract_variant, intron_variant		3

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

GnomAD3 exomes AF: 0.553 AC: 136508 AN: 246832 Hom.: 38538 AF XY: 0.549 AC XY: 73253 AN XY: 133372

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 SAS exome AF: 0.475

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

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.563

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

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.569

Alfa AF: 0.535 Hom.: 11283

Bravo AF: 0.556

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.5
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1805335; hg19: chr9-110081018;