9-107312950-G-T

Position:

• chr9-107312950-G-T

Variant summary

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

The NM_002874.5(RAD23B):​c.553+1213G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,242 control chromosomes in the GnomAD database, including 65,749 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 0.93 (65749 hom., cov: 30)
• Consequence: RAD23B NM_002874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD23B	NM_002874.5	c.553+1213G>T		intron_variant		ENST00000358015.8
RAD23B	NM_001244713.1	c.490+1213G>T		intron_variant
RAD23B	NM_001244724.2	c.337+1213G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD23B	ENST00000358015.8	c.553+1213G>T		intron_variant		1	NM_002874.5	P1
RAD23B	ENST00000416373.6	c.337+1213G>T		intron_variant		1
RAD23B	ENST00000457811.1	c.162+1213G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141229 AN: 152124 Hom.: 65697 Cov.: 30

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.928 AC: 141341 AN: 152242 Hom.: 65749 Cov.: 30 AF XY: 0.930 AC XY: 69202 AN XY: 74436

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.925

Alfa AF: 0.907 Hom.: 25938

Bravo AF: 0.932

Asia WGS AF: 0.949 AC: 3299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.76

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: rs6477569; hg19: chr9-110075231;