chr11-2909210-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_002555.6(SLC22A18):c.257G>A(p.Arg86His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,536,602 control chromosomes in the GnomAD database, including 114 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 0.0034 ( 17 hom., cov: 35)
Exomes 𝑓: 0.0025 ( 97 hom. )
Consequence
SLC22A18
NM_002555.6 missense
NM_002555.6 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: -0.443
Genes affected
SLC22A18 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0030741394).
BP6
?
Variant 11-2909210-G-A is Benign according to our data. Variant chr11-2909210-G-A is described in ClinVar as [Benign]. Clinvar id is 6977.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A18 | NM_002555.6 | c.257G>A | p.Arg86His | missense_variant | 4/11 | ENST00000649076.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A18 | ENST00000649076.2 | c.257G>A | p.Arg86His | missense_variant | 4/11 | NM_002555.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00342 AC: 521AN: 152194Hom.: 17 Cov.: 35
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0144 AC: 1958AN: 135996Hom.: 59 AF XY: 0.0120 AC XY: 903AN XY: 75318
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GnomAD4 exome AF: 0.00247 AC: 3417AN: 1384292Hom.: 97 Cov.: 36 AF XY: 0.00235 AC XY: 1604AN XY: 683808
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GnomAD4 genome ? AF: 0.00343 AC: 522AN: 152310Hom.: 17 Cov.: 35 AF XY: 0.00395 AC XY: 294AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rhabdomyosarcoma, somatic Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 31, 1998 | - - |
SLC22A18-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 04, 2020 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.
MutationTaster
Benign
D;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N;N
REVEL
Benign
Sift
Benign
T;T;.;T;T
Sift4G
Benign
T;T;.;T;T
Polyphen
B;B;B;B;.
Vest4
MPC
0.21
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at