6-117311039-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001378902.1(ROS1):c.6196C>T(p.Arg2066Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000342 in 1,608,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
ROS1
NM_001378902.1 missense
NM_001378902.1 missense
Scores
2
10
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.91
Genes affected
ROS1 (HGNC:10261): (ROS proto-oncogene 1, receptor tyrosine kinase) This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26843768).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROS1 | NM_001378902.1 | c.6196C>T | p.Arg2066Trp | missense_variant | 40/44 | ENST00000368507.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROS1 | ENST00000368507.8 | c.6196C>T | p.Arg2066Trp | missense_variant | 40/44 | 5 | NM_001378902.1 | P1 | |
ROS1 | ENST00000368508.7 | c.6214C>T | p.Arg2072Trp | missense_variant | 39/43 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 151984Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
9
AN:
151984
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000843 AC: 21AN: 249140Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134716
GnomAD3 exomes
AF:
AC:
21
AN:
249140
Hom.:
AF XY:
AC XY:
16
AN XY:
134716
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000316 AC: 46AN: 1456442Hom.: 0 Cov.: 29 AF XY: 0.0000455 AC XY: 33AN XY: 724758
GnomAD4 exome
AF:
AC:
46
AN:
1456442
Hom.:
Cov.:
29
AF XY:
AC XY:
33
AN XY:
724758
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74358
GnomAD4 genome
AF:
AC:
9
AN:
152102
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74358
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
8
Asia WGS
AF:
AC:
1
AN:
3476
EpiCase
AF:
EpiControl
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at