Variant 12-110515087-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001286535.2(RAD9B):c.526C>G(p.Gln176Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00293 in 1,556,146 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 16 hom. )

Consequence

RAD9B
NM_001286535.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

RAD9B (HGNC:21700): (RAD9 checkpoint clamp component B) Predicted to be involved in DNA integrity checkpoint signaling; DNA repair; and cellular response to ionizing radiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RAD9B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011726439).

BP6

Variant 12-110515087-C-G is Benign according to our data. Variant chr12-110515087-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3037766.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00241 (367/152240) while in subpopulation NFE AF= 0.00444 (302/68028). AF 95% confidence interval is 0.00403. There are 0 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD9B	NM_001286535.2 link	c.526C>G	p.Gln176Glu	missense_variant	6/11	ENST00000409300.6	NP_001273464.1	Q6WBX8B4DX60

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD9B	ENST00000409300.6 link	c.526C>G	p.Gln176Glu	missense_variant	6/11	1	NM_001286535.2	ENSP00000386434.1		B4DX60

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

367

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00227

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00444

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00203

AC:

345

AN:

170004

Hom.:

AF XY:

0.00178

AC XY:

159

AN XY:

89174

show subpopulations

Gnomad AFR exome

AF:

0.000582

Gnomad AMR exome

AF:

0.000395

Gnomad ASJ exome

AF:

0.000678

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00248

Gnomad NFE exome

AF:

0.00403

Gnomad OTH exome

AF:

0.00169

GnomAD4 exome

AF:

0.00299

AC:

4198

AN:

1403906

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

2086

AN XY:

692884

show subpopulations

Gnomad4 AFR exome

AF:

0.000624

Gnomad4 AMR exome

AF:

0.000387

Gnomad4 ASJ exome

AF:

0.000908

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00359

Gnomad4 NFE exome

AF:

0.00359

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152240

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00227

Gnomad4 NFE

AF:

0.00444

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.00203

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00280

AC:

ExAC

AF:

0.00112

AC:

126

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAD9B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

.;.;T;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

.;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.33

T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.99

.;.;D;.

Vest4

0.56

MVP

0.77

MPC

0.15

ClinPred

0.040

GERP RS

5.8

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over