Variant 6-117288553-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001378902.1(ROS1):c.6965A>G(p.Lys2322Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,614,120 control chromosomes in the GnomAD database, including 7 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 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 3 hom. )

Consequence

ROS1
NM_001378902.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018203557).

BP6

Variant 6-117288553-T-C is Benign according to our data. Variant chr6-117288553-T-C is described in ClinVar as [Benign]. Clinvar id is 782476.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROS1	NM_001378902.1 linkuse as main transcript	c.6965A>G	p.Lys2322Arg	missense_variant	44/44	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.6965A>G	p.Lys2322Arg	missense_variant	44/44	5	NM_001378902.1	ENSP00000357493.3		Q5H8Y1
ROS1	ENST00000368508.7 linkuse as main transcript	c.6983A>G	p.Lys2328Arg	missense_variant	43/43	1		ENSP00000357494.3		P08922

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00106

AC:

267

AN:

251208

Hom.:

AF XY:

0.000796

AC XY:

108

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00130

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000390

AC:

570

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

255

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00406

AC:

618

AN:

152326

Hom.:

Cov.:

AF XY:

0.00413

AC XY:

308

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000716

Hom.:

Bravo

AF:

0.00453

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00140

AC:

170

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.2

DANN

Benign

0.90

DEOGEN2

Benign

0.081

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.15

Sift

Benign

0.64

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.15

B;.

Vest4

0.044

MVP

0.18

MPC

0.023

ClinPred

0.0021

GERP RS

-0.28

Varity_R

0.027

gMVP

0.13

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.

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