rs11922749

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020165.4(RAD18):​c.704+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 978,598 control chromosomes in the GnomAD database, including 294 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 0.026 ( 175 hom., cov: 32)
Exomes 𝑓: 0.0029 ( 119 hom. )

Consequence

RAD18
NM_020165.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAD18NM_020165.4 linkuse as main transcriptc.704+96C>T intron_variant ENST00000264926.7
RAD18XM_017006873.2 linkuse as main transcriptc.446+96C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAD18ENST00000264926.7 linkuse as main transcriptc.704+96C>T intron_variant 1 NM_020165.4 P1
RAD18ENST00000415439.5 linkuse as main transcriptc.704+96C>T intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0259
AC:
3942
AN:
151970
Hom.:
174
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0887
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0128
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000324
Gnomad OTH
AF:
0.0229
GnomAD4 exome
AF:
0.00288
AC:
2378
AN:
826510
Hom.:
119
AF XY:
0.00242
AC XY:
1030
AN XY:
425898
show subpopulations
Gnomad4 AFR exome
AF:
0.0934
Gnomad4 AMR exome
AF:
0.00683
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000323
Gnomad4 FIN exome
AF:
0.0000207
Gnomad4 NFE exome
AF:
0.000208
Gnomad4 OTH exome
AF:
0.00696
GnomAD4 genome
AF:
0.0260
AC:
3948
AN:
152088
Hom.:
175
Cov.:
32
AF XY:
0.0247
AC XY:
1838
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.0886
Gnomad4 AMR
AF:
0.0128
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000324
Gnomad4 OTH
AF:
0.0227
Alfa
AF:
0.0243
Hom.:
20
Bravo
AF:
0.0305
Asia WGS
AF:
0.00433
AC:
16
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
3.1
DANN
Benign
0.35

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.

Other links and lift over

dbSNP: rs11922749; hg19: chr3-8981142; API