rs2243379

Variant names:

• chr6-117403299-C-A
• rs2243379
• NM_001378902.1:c.466-22G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378902.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROS1	NM_001378902.1	MANE Select	c.466-22G>T		intron	N/A	NP_001365831.1
	ROS1	NM_002944.3		c.439-22G>T		intron	N/A	NP_002935.2
	ROS1	NM_001378891.1		c.466-22G>T		intron	N/A	NP_001365820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROS1	ENST00000368507.8	TSL:5 MANE Select	c.466-22G>T		intron	N/A	ENSP00000357493.3
	ROS1	ENST00000368508.7	TSL:1	c.439-22G>T		intron	N/A	ENSP00000357494.3
	ENSG00000282218	ENST00000467125.1	TSL:2	c.548-81905G>T		intron	N/A	ENSP00000487717.1

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

GnomAD2 exomes AF: 0.528 AC: 127471 AN: 241424 AF XY: 0.526

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 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

African (AFR) AF: 0.889 AC: 29123 AN: 32762

American (AMR) AF: 0.464 AC: 19692 AN: 42472

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 10430 AN: 25856

East Asian (EAS) AF: 0.562 AC: 22205 AN: 39488

South Asian (SAS) AF: 0.658 AC: 55323 AN: 84070

European-Finnish (FIN) AF: 0.602 AC: 32044 AN: 53262

Middle Eastern (MID) AF: 0.528 AC: 2901 AN: 5492

European-Non Finnish (NFE) AF: 0.456 AC: 504632 AN: 1106634

Other (OTH) AF: 0.514 AC: 30862 AN: 59988

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

African (AFR) AF: 0.872 AC: 36193 AN: 41512

American (AMR) AF: 0.493 AC: 7542 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2852 AN: 5152

South Asian (SAS) AF: 0.679 AC: 3271 AN: 4820

European-Finnish (FIN) AF: 0.610 AC: 6433 AN: 10544

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31752 AN: 67956

Other (OTH) AF: 0.581 AC: 1222 AN: 2104

Alfa AF: 0.496 Hom.: 57389

Bravo AF: 0.599

Asia WGS AF: 0.640 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-0.096
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2243379; hg19: chr6-117724462; COSMIC: COSV63855806;