Variant 6-117301068-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001378902.1(ROS1):c.6621C>A(p.Asp2207Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,606,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

ROS1
NM_001378902.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.265

Variant links:

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]

ROS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008882403).

BP6

Variant 6-117301068-G-T is Benign according to our data. Variant chr6-117301068-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2673077.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROS1	NM_001378902.1 linkuse as main transcript	c.6621C>A	p.Asp2207Glu	missense_variant	43/44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8 linkuse as main transcript	c.6621C>A	p.Asp2207Glu	missense_variant	43/44	5	NM_001378902.1	ENSP00000357493.3		Q5H8Y1
ROS1	ENST00000368508.7 linkuse as main transcript	c.6639C>A	p.Asp2213Glu	missense_variant	42/43	1		ENSP00000357494.3		P08922

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00558

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000643

AC:

158

AN:

245812

Hom.:

AF XY:

0.000624

AC XY:

AN XY:

132942

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00340

Gnomad EAS exome

AF:

0.00650

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000214

AC:

311

AN:

1454712

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

158

AN XY:

723224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00265

Gnomad4 EAS exome

AF:

0.00475

Gnomad4 SAS exome

AF:

0.0000595

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000902

Gnomad4 OTH exome

AF:

0.000632

GnomAD4 genome

AF:

0.000335

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000442

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000568

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

ROS1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.0089

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.49

N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.31

N;N

REVEL

Benign

0.23

Sift

Benign

0.54

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0040

B;.

Vest4

0.10

MutPred

0.11

Loss of helix (P = 0.2022);.;

MVP

0.32

MPC

0.027

ClinPred

0.018

GERP RS

1.1

Varity_R

0.14

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over