rs1805327

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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

Publications

21 publications found

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:26355): (tetratricopeptide repeat domain 23 like) Predicted to be located in cytoplasm; microtubule cytoskeleton; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

TTC23L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD1	NM_002853.4	MANE Select	c.842A>G	p.Glu281Gly	missense	Exon 6 of 6	NP_002844.1	O60671-1
RAD1	NR_026591.2		n.891A>G		non_coding_transcript_exon	Exon 5 of 5
TTC23L	NR_169875.1		n.974-9592T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD1	ENST00000382038.7	TSL:1 MANE Select	c.842A>G	p.Glu281Gly	missense	Exon 6 of 6	ENSP00000371469.2	O60671-1
RAD1	ENST00000325577.8	TSL:1	n.*526A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000313467.4	O60671-3
RAD1	ENST00000325577.8	TSL:1	n.*526A>G		3_prime_UTR	Exon 5 of 5	ENSP00000313467.4	O60671-3

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

GnomAD2 exomes

AF:

0.0686

AC:

16609

AN:

242188

AF XY:

0.0744

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 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

African (AFR)

AF:

0.0112

AC:

364

AN:

32504

American (AMR)

AF:

0.0368

AC:

1509

AN:

40988

Ashkenazi Jewish (ASJ)

AF:

0.0880

AC:

2261

AN:

25684

East Asian (EAS)

AF:

0.0352

AC:

1392

AN:

39520

South Asian (SAS)

AF:

0.122

AC:

10350

AN:

85016

European-Finnish (FIN)

AF:

0.0731

AC:

3896

AN:

53308

Middle Eastern (MID)

AF:

0.0629

AC:

278

AN:

4420

European-Non Finnish (NFE)

AF:

0.0736

AC:

81512

AN:

1106822

Other (OTH)

AF:

0.0678

AC:

4051

AN:

59748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

4435

8870

13305

17740

22175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3014

6028

9042

12056

15070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0541

AC:

8236

AN:

152252

Hom.:

313

Cov.:

AF XY:

0.0547

AC XY:

4070

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0125

AC:

519

AN:

41560

American (AMR)

AF:

0.0466

AC:

713

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0957

AC:

332

AN:

3470

East Asian (EAS)

AF:

0.0330

AC:

171

AN:

5184

South Asian (SAS)

AF:

0.114

AC:

548

AN:

4818

European-Finnish (FIN)

AF:

0.0687

AC:

728

AN:

10598

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0739

AC:

5028

AN:

68012

Other (OTH)

AF:

0.0606

AC:

128

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

393

786

1178

1571

1964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0582

Hom.:

269

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

RAD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

0.0078

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

3.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.81

REVEL

Benign

0.076

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0090

Polyphen

0.099

Vest4

0.076

MPC

0.12

ClinPred

0.022

GERP RS

5.7

Varity_R

0.051

gMVP

0.29

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over