chr6-117321368-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001378902.1(ROS1):c.5650A>G(p.Lys1884Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,612,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

ROS1
NM_001378902.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.91

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
breast cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ROS1 links:

ENSG00000282218 (HGNC:):

ENSG00000282218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055877566).

BP6

Variant 6-117321368-T-C is Benign according to our data. Variant chr6-117321368-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 731099.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378902.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ROS1	NM_001378902.1	MANE Select	c.5650A>G	p.Lys1884Glu	missense	Exon 36 of 44	NP_001365831.1	Q5H8Y1
ROS1	NM_002944.3		c.5668A>G	p.Lys1890Glu	missense	Exon 35 of 43	NP_002935.2
ROS1	NM_001378891.1		c.5656A>G	p.Lys1886Glu	missense	Exon 36 of 44	NP_001365820.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ROS1	ENST00000368507.8	TSL:5 MANE Select	c.5650A>G	p.Lys1884Glu	missense	Exon 36 of 44	ENSP00000357493.3	Q5H8Y1
ROS1	ENST00000368508.7	TSL:1	c.5668A>G	p.Lys1890Glu	missense	Exon 35 of 43	ENSP00000357494.3	P08922
ENSG00000282218	ENST00000467125.1	TSL:2	c.574A>G	p.Lys192Glu	missense	Exon 5 of 7	ENSP00000487717.1	A0A0J9YVX5

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000276

AC:

AN:

249688

AF XY:

0.000104

show subpopulations

Gnomad AFR exome

AF:

0.00370

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000719

AC:

105

AN:

1460660

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

726642

show subpopulations

African (AFR)

AF:

0.00239

AC:

AN:

33404

American (AMR)

AF:

0.000180

AC:

AN:

44434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111546

Other (OTH)

AF:

0.000182

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152298

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

41580

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000450

Hom.:

Bravo

AF:

0.000793

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000305

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

0.030

Eigen_PC

Benign

-0.010

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.70

M_CAP

Benign

0.028

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.8

PhyloP100

3.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Benign

0.18

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0060

Polyphen

0.80

Vest4

0.24

MVP

0.42

MPC

0.033

ClinPred

0.081

GERP RS

3.7

Varity_R

0.22

gMVP

0.44

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over