Variant 6-117301070-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378902.1(ROS1):c.6619G>A(p.Asp2207Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,602,860 control chromosomes in the GnomAD database, including 47,546 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3241 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44305 hom. )

Consequence

ROS1
NM_001378902.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.924

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026458502).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROS1	NM_001378902.1 linkuse as main transcript	c.6619G>A	p.Asp2207Asn	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.6619G>A	p.Asp2207Asn	missense_variant	43/44	5	NM_001378902.1	ENSP00000357493.3		Q5H8Y1
ROS1	ENST00000368508.7 linkuse as main transcript	c.6637G>A	p.Asp2213Asn	missense_variant	42/43	1		ENSP00000357494.3		P08922

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28437

AN:

151986

Hom.:

3244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0575

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.203

AC:

49500

AN:

243942

Hom.:

5539

AF XY:

0.205

AC XY:

27110

AN XY:

131964

show subpopulations

Gnomad AFR exome

AF:

0.0548

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.241

AC:

349551

AN:

1450756

Hom.:

44305

Cov.:

AF XY:

0.239

AC XY:

172022

AN XY:

721242

show subpopulations

Gnomad4 AFR exome

AF:

0.0508

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.225

GnomAD4 genome

AF:

0.187

AC:

28437

AN:

152104

Hom.:

3241

Cov.:

AF XY:

0.184

AC XY:

13670

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0575

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.239

Hom.:

11728

Bravo

AF:

0.176

TwinsUK

AF:

0.249

AC:

925

ALSPAC

AF:

0.257

AC:

989

ESP6500AA

AF:

0.0688

AC:

303

ESP6500EA

AF:

0.259

AC:

2231

ExAC

AF:

0.208

AC:

25274

Asia WGS

AF:

0.154

AC:

537

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.89

L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.16

Sift

Benign

0.18

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0090

B;.

Vest4

0.14

MPC

0.031

ClinPred

0.013

GERP RS

3.2

Varity_R

0.25

gMVP

0.32

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over