rs1321807

Variant names:

• chr6-117363829-A-G
• rs1321807
• NM_001378902.1:c.3104-964T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-117363829-A-G
• chr6-117363829-A-T

Variant summary

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

The ENST00000467125.1(ENSG00000282218):​c.548-42435T>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: ENSG00000282218 ENST00000467125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000467125.1. 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.3104-964T>C		intron	N/A	NP_001365831.1
	ROS1	NM_002944.3		c.3119-964T>C		intron	N/A	NP_002935.2
	ROS1	NM_001378891.1		c.3107-964T>C		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.3104-964T>C		intron	N/A	ENSP00000357493.3
	ROS1	ENST00000368508.7	TSL:1	c.3119-964T>C		intron	N/A	ENSP00000357494.3
	ENSG00000282218	ENST00000467125.1	TSL:2	c.548-42435T>C		intron	N/A	ENSP00000487717.1

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

African (AFR) AF: 0.690 AC: 28562 AN: 41402

American (AMR) AF: 0.593 AC: 9020 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3059 AN: 5146

South Asian (SAS) AF: 0.586 AC: 2814 AN: 4806

European-Finnish (FIN) AF: 0.561 AC: 5907 AN: 10528

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33577 AN: 67906

Other (OTH) AF: 0.559 AC: 1179 AN: 2108

Alfa AF: 0.516 Hom.: 80454

Bravo AF: 0.572

Asia WGS AF: 0.580 AC: 2014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.54
PhyloP100		-0.45
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: rs1321807; hg19: chr6-117684992;