6-117322270-T-C

Position:

• chr6-117322270-T-C

Variant summary

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

The NM_001378902.1(ROS1):​c.5624-876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,098 control chromosomes in the GnomAD database, including 1,094 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 0.11 (1094 hom., cov: 32)
• Consequence: ROS1 NM_001378902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390

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]

ENSG00000282218 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.5624-876A>G		intron_variant		ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.5624-876A>G		intron_variant		5	NM_001378902.1	ENSP00000357493.3
ROS1	ENST00000368508.7	c.5642-876A>G		intron_variant		1		ENSP00000357494.3
ENSG00000282218	ENST00000467125.1	c.548-876A>G		intron_variant		2		ENSP00000487717.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17440 AN: 151980 Hom.: 1095 Cov.: 32

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.115 AC: 17452 AN: 152098 Hom.: 1094 Cov.: 32 AF XY: 0.114 AC XY: 8505 AN XY: 74342

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.125

Alfa AF: 0.127 Hom.: 673

Bravo AF: 0.116

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.61

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: rs492132; hg19: chr6-117643433; COSMIC: COSV63853923;