chr9-107285035-A-G

Position:

• chr9-107285035-A-G

Variant summary

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

The NM_002874.5(RAD23B):​c.66+1340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,093,090 control chromosomes in the GnomAD database, including 263,288 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 0.75 (43561 hom., cov: 33)
  • Exomes 𝑓: 0.68 (219727 hom.)
• Consequence: RAD23B NM_002874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.966

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD23B	NM_002874.5	c.66+1340A>G		intron_variant		ENST00000358015.8
RAD23B	NM_001244713.1	c.3+122A>G		intron_variant
RAD23B	NM_001244724.2	c.-151+848A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD23B	ENST00000358015.8	c.66+1340A>G		intron_variant		1	NM_002874.5	P1
RAD23B	ENST00000416373.6	c.-151+848A>G		intron_variant		1
RAD23B	ENST00000419616.5	c.66+1340A>G		intron_variant		3
RAD23B	ENST00000442587.1	c.3+122A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113747 AN: 152050 Hom.: 43505 Cov.: 33

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.681 AC: 640792 AN: 940922 Hom.: 219727 AF XY: 0.679 AC XY: 313916 AN XY: 462072

Gnomad4 AFR exome AF: 0.937

Gnomad4 AMR exome AF: 0.639

Gnomad4 ASJ exome AF: 0.764

Gnomad4 EAS exome AF: 0.765

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.681

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.748 AC: 113863 AN: 152168 Hom.: 43561 Cov.: 33 AF XY: 0.746 AC XY: 55513 AN XY: 74378

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.763

Alfa AF: 0.698 Hom.: 4691

Bravo AF: 0.758

Asia WGS AF: 0.728 AC: 2528 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.45

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: rs10739234; hg19: chr9-110047316; COSMIC: COSV63658613;