12-88046899-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001009894.3(RLIG1):​c.712G>C​(p.Val238Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,611,880 control chromosomes in the GnomAD database, including 272,810 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 20986 hom., cov: 31)
Exomes 𝑓: 0.58 ( 251824 hom. )

Consequence

RLIG1
NM_001009894.3 missense

Scores

17

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16

Publications

36 publications found
Variant links:
Genes affected
RLIG1 (HGNC:25322): (RNA 5'-phosphate and 3'-OH ligase 1) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=7.9659065E-7).
BP6
Variant 12-88046899-G-C is Benign according to our data. Variant chr12-88046899-G-C is described in ClinVar as [Benign]. Clinvar id is 3910981.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RLIG1NM_001009894.3 linkc.712G>C p.Val238Leu missense_variant Exon 6 of 7 ENST00000356891.4 NP_001009894.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RLIG1ENST00000356891.4 linkc.712G>C p.Val238Leu missense_variant Exon 6 of 7 1 NM_001009894.3 ENSP00000349358.3 Q8N999-1

Frequencies

GnomAD3 genomes
AF:
0.497
AC:
75318
AN:
151686
Hom.:
20982
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.228
Gnomad AMI
AF:
0.459
Gnomad AMR
AF:
0.552
Gnomad ASJ
AF:
0.649
Gnomad EAS
AF:
0.731
Gnomad SAS
AF:
0.628
Gnomad FIN
AF:
0.594
Gnomad MID
AF:
0.680
Gnomad NFE
AF:
0.596
Gnomad OTH
AF:
0.543
GnomAD2 exomes
AF:
0.589
AC:
147567
AN:
250530
AF XY:
0.596
show subpopulations
Gnomad AFR exome
AF:
0.220
Gnomad AMR exome
AF:
0.601
Gnomad ASJ exome
AF:
0.652
Gnomad EAS exome
AF:
0.759
Gnomad FIN exome
AF:
0.593
Gnomad NFE exome
AF:
0.600
Gnomad OTH exome
AF:
0.601
GnomAD4 exome
AF:
0.583
AC:
851547
AN:
1460076
Hom.:
251824
Cov.:
39
AF XY:
0.586
AC XY:
425638
AN XY:
726326
show subpopulations
African (AFR)
AF:
0.217
AC:
7258
AN:
33426
American (AMR)
AF:
0.596
AC:
26539
AN:
44558
Ashkenazi Jewish (ASJ)
AF:
0.644
AC:
16796
AN:
26072
East Asian (EAS)
AF:
0.656
AC:
26029
AN:
39654
South Asian (SAS)
AF:
0.607
AC:
52212
AN:
86032
European-Finnish (FIN)
AF:
0.594
AC:
31682
AN:
53378
Middle Eastern (MID)
AF:
0.654
AC:
3764
AN:
5758
European-Non Finnish (NFE)
AF:
0.587
AC:
652169
AN:
1110876
Other (OTH)
AF:
0.582
AC:
35098
AN:
60322
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
16620
33240
49860
66480
83100
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
17830
35660
53490
71320
89150
<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:
0.496
AC:
75327
AN:
151804
Hom.:
20986
Cov.:
31
AF XY:
0.502
AC XY:
37202
AN XY:
74176
show subpopulations
African (AFR)
AF:
0.228
AC:
9424
AN:
41418
American (AMR)
AF:
0.551
AC:
8406
AN:
15246
Ashkenazi Jewish (ASJ)
AF:
0.649
AC:
2249
AN:
3466
East Asian (EAS)
AF:
0.731
AC:
3768
AN:
5156
South Asian (SAS)
AF:
0.630
AC:
3031
AN:
4814
European-Finnish (FIN)
AF:
0.594
AC:
6244
AN:
10506
Middle Eastern (MID)
AF:
0.687
AC:
202
AN:
294
European-Non Finnish (NFE)
AF:
0.596
AC:
40435
AN:
67894
Other (OTH)
AF:
0.548
AC:
1152
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1704
3408
5111
6815
8519
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
670
1340
2010
2680
3350
<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:
0.577
Hom.:
18392
Bravo
AF:
0.482
TwinsUK
AF:
0.588
AC:
2179
ALSPAC
AF:
0.592
AC:
2280
ESP6500AA
AF:
0.236
AC:
1038
ESP6500EA
AF:
0.589
AC:
5064
ExAC
AF:
0.583
AC:
70725
Asia WGS
AF:
0.604
AC:
2099
AN:
3478
EpiCase
AF:
0.604
EpiControl
AF:
0.609

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 16, 2025
Laboratory of Genetics, Children's Clinical University Hospital Latvia
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.046
BayesDel_addAF
Benign
-0.84
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.48
DANN
Benign
0.73
DEOGEN2
Benign
0.017
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.036
N
LIST_S2
Benign
0.21
T
MetaRNN
Benign
8.0e-7
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.4
N
PhyloP100
-1.2
PROVEAN
Benign
0.97
N
REVEL
Benign
0.036
Sift
Benign
0.56
T
Sift4G
Benign
0.46
T
Polyphen
0.0
B
Vest4
0.055
MutPred
0.082
Gain of catalytic residue at V238 (P = 0.011);
MPC
0.20
ClinPred
0.00071
T
GERP RS
-4.2
Varity_R
0.020
gMVP
0.35
Mutation Taster
=98/2
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs9262; hg19: chr12-88440676; COSMIC: COSV58354252; COSMIC: COSV58354252; API