chr6-117322969-C-T

Variant names:

• chr6-117322969-C-T
• rs575006
• NM_001378902.1:c.5623+1363G>A

Variant summary

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

The NM_001378902.1(ROS1):​c.5623+1363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 152,122 control chromosomes in the GnomAD database, including 873 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 0.095 (873 hom., cov: 32)
• Consequence: ROS1 NM_001378902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROS1	NM_001378902.1	MANE Select	c.5623+1363G>A		intron	N/A	NP_001365831.1	Q5H8Y1
	ROS1	NM_002944.3		c.5641+1363G>A		intron	N/A	NP_002935.2
	ROS1	NM_001378891.1		c.5629+1363G>A		intron	N/A	NP_001365820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROS1	ENST00000368507.8	TSL:5 MANE Select	c.5623+1363G>A		intron	N/A	ENSP00000357493.3	Q5H8Y1
	ROS1	ENST00000368508.7	TSL:1	c.5641+1363G>A		intron	N/A	ENSP00000357494.3	P08922
	ENSG00000282218	ENST00000467125.1	TSL:2	c.548-1575G>A		intron	N/A	ENSP00000487717.1	A0A0J9YVX5

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14395 AN: 152004 Hom.: 875 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0947 AC: 14401 AN: 152122 Hom.: 873 Cov.: 32 AF XY: 0.0943 AC XY: 7009 AN XY: 74348

African (AFR) AF: 0.0236 AC: 980 AN: 41510

American (AMR) AF: 0.0886 AC: 1354 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3470

East Asian (EAS) AF: 0.118 AC: 609 AN: 5152

South Asian (SAS) AF: 0.111 AC: 536 AN: 4818

European-Finnish (FIN) AF: 0.111 AC: 1172 AN: 10568

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8643 AN: 68006

Other (OTH) AF: 0.107 AC: 226 AN: 2112

Alfa AF: 0.0994 Hom.: 115

Bravo AF: 0.0906

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.45
PhyloP100		0.60
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: rs575006; hg19: chr6-117644132;