rs2243379

Positions:

• chr6-117403299-C-A
• chr6-117403299-C-T

Variant summary

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

The NM_001378902.1(ROS1):​c.466-22G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,602,072 control chromosomes in the GnomAD database, including 208,226 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 0.60 (29847 hom., cov: 32)
  • Exomes 𝑓: 0.49 (178379 hom.)
• Consequence: ROS1 NM_001378902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROS1	NM_001378902.1	c.466-22G>T		intron_variant		ENST00000368507.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROS1	ENST00000368507.8	c.466-22G>T		intron_variant		5	NM_001378902.1	P1
ROS1	ENST00000368508.7	c.439-22G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91227 AN: 151930 Hom.: 29800 Cov.: 32

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.582

GnomAD3 exomes AF: 0.528 AC: 127471 AN: 241424 Hom.: 35366 AF XY: 0.526 AC XY: 68501 AN XY: 130286

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.565

Gnomad SAS exome AF: 0.657

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.488 AC: 707212 AN: 1450024 Hom.: 178379 Cov.: 32 AF XY: 0.491 AC XY: 354052 AN XY: 721034

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.601 AC: 91333 AN: 152048 Hom.: 29847 Cov.: 32 AF XY: 0.606 AC XY: 45057 AN XY: 74294

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.581

Alfa AF: 0.466 Hom.: 30865

Bravo AF: 0.599

Asia WGS AF: 0.640 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2243379; hg19: chr6-117724462; COSMIC: COSV63855806;