rs10978792

Positions:

• chr9-107320832-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002874.5(RAD23B):​c.682-1151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 152,304 control chromosomes in the GnomAD database, including 81 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 0.026 (81 hom., cov: 32)
• Consequence: RAD23B NM_002874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0265 (4030/152304) while in subpopulation NFE AF= 0.0399 (2712/68014). AF 95% confidence interval is 0.0386. There are 81 homozygotes in gnomad4. There are 1967 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4030 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD23B	NM_002874.5	c.682-1151A>G		intron_variant		ENST00000358015.8	NP_002865.1
RAD23B	NM_001244713.1	c.619-1151A>G		intron_variant			NP_001231642.1
RAD23B	NM_001244724.2	c.466-1151A>G		intron_variant			NP_001231653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8	c.682-1151A>G		intron_variant		1	NM_002874.5	ENSP00000350708	P1
RAD23B	ENST00000416373.6	c.466-1151A>G		intron_variant		1		ENSP00000405623
RAD23B	ENST00000457811.1	c.290+1953A>G		intron_variant		3		ENSP00000396975

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4029 AN: 152186 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.00651

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0265 AC: 4030 AN: 152304 Hom.: 81 Cov.: 32 AF XY: 0.0264 AC XY: 1967 AN XY: 74474

Gnomad4 AFR AF: 0.00649

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0352 Hom.: 51

Bravo AF: 0.0243

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.60

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: rs10978792; hg19: chr9-110083113;