5-34908772-T-C

Position:

chr5-34908772-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002853.4(RAD1):c.842A>G(p.Glu281Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 1,600,262 control chromosomes in the GnomAD database, including 4,655 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.054 ( 313 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4342 hom. )

Consequence

RAD1
NM_002853.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

RAD1 (HGNC:9806): (RAD1 checkpoint DNA exonuclease) This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jan 2009]

RAD1 links:

TTC23L (HGNC:):

TTC23L 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=0.0016051531).

BP6

Variant 5-34908772-T-C is Benign according to our data. Variant chr5-34908772-T-C is described in ClinVar as [Benign]. Clinvar id is 3057114.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAD1	NM_002853.4 linkuse as main transcript	c.842A>G	p.Glu281Gly	missense_variant	6/6	ENST00000382038.7	NP_002844.1
RAD1	NR_026591.2 linkuse as main transcript	n.891A>G		non_coding_transcript_exon_variant	5/5
TTC23L	NR_169875.1 linkuse as main transcript	n.974-9592T>C		intron_variant, non_coding_transcript_variant
TTC23L	NR_169876.1 linkuse as main transcript	n.1048-9592T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD1	ENST00000382038.7 linkuse as main transcript	c.842A>G	p.Glu281Gly	missense_variant	6/6	1	NM_002853.4	ENSP00000371469	P1	O60671-1
RAD1	ENST00000325577.8 linkuse as main transcript	c.*526A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000313467		O60671-3
RAD1	ENST00000341754.8 linkuse as main transcript	c.842A>G	p.Glu281Gly	missense_variant	9/9	5		ENSP00000340879	P1	O60671-1
RAD1	ENST00000513914.5 linkuse as main transcript	c.*687A>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000421007

Frequencies

GnomAD3 genomes

AF:

0.0541

AC:

8233

AN:

152134

Hom.:

313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.0957

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0687

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0739

Gnomad OTH

AF:

0.0589

GnomAD3 exomes

AF:

0.0686

AC:

16609

AN:

242188

Hom.:

723

AF XY:

0.0744

AC XY:

9779

AN XY:

131408

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.0932

Gnomad EAS exome

AF:

0.0350

Gnomad SAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0700

Gnomad NFE exome

AF:

0.0742

Gnomad OTH exome

AF:

0.0724

GnomAD4 exome

AF:

0.0729

AC:

105613

AN:

1448010

Hom.:

4342

Cov.:

AF XY:

0.0749

AC XY:

53992

AN XY:

720508

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.0368

Gnomad4 ASJ exome

AF:

0.0880

Gnomad4 EAS exome

AF:

0.0352

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.0731

Gnomad4 NFE exome

AF:

0.0736

Gnomad4 OTH exome

AF:

0.0678

GnomAD4 genome

AF:

0.0541

AC:

8236

AN:

152252

Hom.:

313

Cov.:

AF XY:

0.0547

AC XY:

4070

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0466

Gnomad4 ASJ

AF:

0.0957

Gnomad4 EAS

AF:

0.0330

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0687

Gnomad4 NFE

AF:

0.0739

Gnomad4 OTH

AF:

0.0606

Alfa

AF:

0.0630

Hom.:

197

Bravo

AF:

0.0498

TwinsUK

AF:

0.0672

AC:

249

ALSPAC

AF:

0.0654

AC:

252

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.0783

AC:

673

ExAC

AF:

0.0679

AC:

8244

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

EpiCase

AF:

0.0756

EpiControl

AF:

0.0715

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 2019

This variant is classified as 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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

T;T

Eigen

Benign

0.0078

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.48

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

0.92

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.81

N;N

REVEL

Benign

0.076

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.099

B;B

Vest4

0.076

MPC

0.12

ClinPred

0.022

GERP RS

5.7

Varity_R

0.051

gMVP

0.29

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