rs1412107750

Variant names:

• chr6-117288800-C-G
• rs1412107750
• NM_001378902.1:c.6718G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-117288800-C-G
• chr6-117288800-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378902.1(ROS1):​c.6718G>C​(p.Glu2240Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2240K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ROS1 NM_001378902.1 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18366209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.6718G>C	p.Glu2240Gln	missense_variant, splice_region_variant	Exon 44 of 44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.6718G>C	p.Glu2240Gln	missense_variant, splice_region_variant	Exon 44 of 44	5	NM_001378902.1	ENSP00000357493.3
ROS1	ENST00000368508.7	c.6736G>C	p.Glu2246Gln	missense_variant, splice_region_variant	Exon 43 of 43	1		ENSP00000357494.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		0.64
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.044
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.40	B;.
Vest4		0.11
MutPred		0.41		Loss of disorder (P = 0.0908);.;
MVP		0.42
MPC		0.031
ClinPred		0.44	T
GERP RS		3.6
Varity_R		0.080
gMVP		0.25
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs1412107750; hg19: chr6-117609963;