rs1321807

Positions:

• chr6-117363829-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.3104-964T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,778 control chromosomes in the GnomAD database, including 25,061 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 0.57 (25061 hom., cov: 31)
• Consequence: ROS1 NM_001378902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROS1	NM_001378902.1	c.3104-964T>C		intron_variant		ENST00000368507.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROS1	ENST00000368507.8	c.3104-964T>C		intron_variant		5	NM_001378902.1	P1
ROS1	ENST00000368508.7	c.3119-964T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86033 AN: 151662 Hom.: 25010 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.568 AC: 86139 AN: 151778 Hom.: 25061 Cov.: 31 AF XY: 0.572 AC XY: 42417 AN XY: 74150

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.559

Alfa AF: 0.503 Hom.: 33364

Bravo AF: 0.572

Asia WGS AF: 0.580 AC: 2014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.54

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: rs1321807; hg19: chr6-117684992;