dbSNP rs2035221: RAD18:c.1169-140G>A (chr3-8899187-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020165.4(RAD18):c.1169-140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 567,726 control chromosomes in the GnomAD database, including 2,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.070 ( 489 hom., cov: 32)

Exomes 𝑓: 0.082 ( 1675 hom. )

Consequence

RAD18
NM_020165.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.325

Publications

1 publications found

Variant links:

Genes affected

RAD18 (HGNC:18278): (RAD18 E3 ubiquitin protein ligase) The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is an ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring-finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens. [provided by RefSeq, Jul 2008]

RAD18 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_020165.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020165.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD18	NM_020165.4	MANE Select	c.1169-140G>A		intron	N/A	NP_064550.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD18	ENST00000264926.7	TSL:1 MANE Select	c.1169-140G>A	intron	N/A	ENSP00000264926.2	Q9NS91
RAD18	ENST00000956589.1		c.1025-140G>A	intron	N/A	ENSP00000626648.1
RAD18	ENST00000858877.1		c.446-140G>A	intron	N/A	ENSP00000528936.1

Frequencies

GnomAD3 genomes

AF:

0.0696

AC:

10589

AN:

152132

Hom.:

486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0614

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0533

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0950

Gnomad OTH

AF:

0.0774

GnomAD4 exome

AF:

0.0818

AC:

33966

AN:

415476

Hom.:

1675

AF XY:

0.0837

AC XY:

17802

AN XY:

212682

show subpopulations

African (AFR)

AF:

0.0230

AC:

257

AN:

11152

American (AMR)

AF:

0.0506

AC:

615

AN:

12166

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

1488

AN:

11710

East Asian (EAS)

AF:

0.0196

AC:

539

AN:

27466

South Asian (SAS)

AF:

0.129

AC:

2659

AN:

20564

European-Finnish (FIN)

AF:

0.0617

AC:

1737

AN:

28160

Middle Eastern (MID)

AF:

0.0751

AC:

133

AN:

1770

European-Non Finnish (NFE)

AF:

0.0881

AC:

24591

AN:

279260

Other (OTH)

AF:

0.0838

AC:

1947

AN:

23228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1453

2906

4360

5813

7266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.0696

AC:

10596

AN:

152250

Hom.:

489

Cov.:

AF XY:

0.0687

AC XY:

5115

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0260

AC:

1081

AN:

41550

American (AMR)

AF:

0.0613

AC:

937

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

483

AN:

3470

East Asian (EAS)

AF:

0.0233

AC:

121

AN:

5188

South Asian (SAS)

AF:

0.141

AC:

678

AN:

4824

European-Finnish (FIN)

AF:

0.0533

AC:

565

AN:

10606

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0950

AC:

6459

AN:

68008

Other (OTH)

AF:

0.0775

AC:

164

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

507

1015

1522

2030

2537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0806

Hom.:

Bravo

AF:

0.0644

Asia WGS

AF:

0.0750

AC:

261

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.6

(source)

DANN

Benign

0.81

PhyloP100

-0.33

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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