rs193920986

Variant names:

• chrX-78273678-AT-A
• rs193920986
• NM_006639.4:c.68delA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006639.4(CYSLTR1):​c.68delA​(p.Asn23IlefsTer10) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CYSLTR1 NM_006639.4 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.97
• Publications: 0 publications found

Genes affected

CYSLTR1 (HGNC:17451): (cysteinyl leukotriene receptor 1) This gene encodes a member of the G-protein coupled receptor 1 family. The encoded protein is a receptor for cysteinyl leukotrienes, and is involved in mediating bronchoconstriction via activation of a phosphatidylinositol-calcium second messenger system. Activation of the encoded receptor results in contraction and proliferation of bronchial smooth muscle cells, eosinophil migration, and damage to the mucus layer in the lung. Upregulation of this gene is associated with asthma and dysregulation may also be implicated in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006639.4. 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
	CYSLTR1	NM_006639.4	MANE Select	c.68delA	p.Asn23IlefsTer10	frameshift	Exon 3 of 3	NP_006630.1
	CYSLTR1	NM_001282186.2		c.68delA	p.Asn23IlefsTer10	frameshift	Exon 2 of 2	NP_001269115.1
	CYSLTR1	NM_001282187.2		c.68delA	p.Asn23IlefsTer10	frameshift	Exon 4 of 4	NP_001269116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR1	ENST00000373304.4	TSL:1 MANE Select	c.68delA	p.Asn23IlefsTer10	frameshift	Exon 3 of 3	ENSP00000362401.3
	CYSLTR1	ENST00000614798.1	TSL:1	c.68delA	p.Asn23IlefsTer10	frameshift	Exon 2 of 2	ENSP00000478492.1
	CYSLTR1	ENST00000856868.1		c.68delA	p.Asn23IlefsTer10	frameshift	Exon 4 of 4	ENSP00000526927.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0

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: rs193920986; hg19: chrX-77529175; COSMIC: COSV64819699;