rs17079156

Positions:

• chr6-117419105-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378902.1(ROS1):​c.124-599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,178 control chromosomes in the GnomAD database, including 1,306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1306 hom., cov: 32)
• Consequence: ROS1 NM_001378902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROS1	NM_001378902.1	c.124-599T>C		intron_variant		ENST00000368507.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROS1	ENST00000368507.8	c.124-599T>C		intron_variant		5	NM_001378902.1	P1
ROS1	ENST00000368508.7	c.124-599T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18996 AN: 152060 Hom.: 1302 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 19024 AN: 152178 Hom.: 1306 Cov.: 32 AF XY: 0.124 AC XY: 9237 AN XY: 74412

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.102

Alfa AF: 0.129 Hom.: 237

Bravo AF: 0.118

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs17079156; hg19: chr6-117740268; COSMIC: COSV63860932;