rs9320599

Variant names:

• chr6-117419303-T-C
• rs9320599
• NM_001378902.1:c.124-797A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378902.1(ROS1):​c.124-797A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 152,264 control chromosomes in the GnomAD database, including 350 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 0.056 (350 hom., cov: 32)
• Consequence: ROS1 NM_001378902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 1 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

ENSG00000282218 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.124-797A>G		intron_variant	Intron 1 of 43	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.124-797A>G		intron_variant	Intron 1 of 43	5	NM_001378902.1	ENSP00000357493.3
ROS1	ENST00000368508.7	c.124-797A>G		intron_variant	Intron 1 of 42	1		ENSP00000357494.3
ENSG00000282218	ENST00000467125.1	c.548-97909A>G		intron_variant	Intron 4 of 6	2		ENSP00000487717.1

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8551 AN: 152146 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0647

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

GnomAD4 genome AF: 0.0562 AC: 8563 AN: 152264 Hom.: 350 Cov.: 32 AF XY: 0.0596 AC XY: 4435 AN XY: 74464

African (AFR) AF: 0.0819 AC: 3402 AN: 41554

American (AMR) AF: 0.0878 AC: 1341 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3472

East Asian (EAS) AF: 0.150 AC: 774 AN: 5170

South Asian (SAS) AF: 0.107 AC: 518 AN: 4830

European-Finnish (FIN) AF: 0.0480 AC: 510 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1783 AN: 68020

Other (OTH) AF: 0.0654 AC: 138 AN: 2110

Alfa AF: 0.0383 Hom.: 243

Bravo AF: 0.0595

Asia WGS AF: 0.136 AC: 470 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	3.1
DANN	Benign	0.44
PhyloP100		0.053
Mutation Taster		=100/0	polymorphism (auto)

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: rs9320599; hg19: chr6-117740466;