X-78272988-AC-GG

Variant names:

• chrX-78272988-AC-GG
• NM_006639.4:c.758_759delGTinsCC
• CYSLTR1 p.Arg253Pro

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_006639.4(CYSLTR1):​c.758_759delGTinsCC​(p.Arg253Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R253H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CYSLTR1 NM_006639.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.70
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR1	NM_006639.4	MANE Select	c.758_759delGTinsCC	p.Arg253Pro	missense	N/A	NP_006630.1	Q9Y271
	CYSLTR1	NM_001282186.2		c.758_759delGTinsCC	p.Arg253Pro	missense	N/A	NP_001269115.1	Q9Y271
	CYSLTR1	NM_001282187.2		c.758_759delGTinsCC	p.Arg253Pro	missense	N/A	NP_001269116.1	Q9Y271

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR1	ENST00000373304.4	TSL:1 MANE Select	c.758_759delGTinsCC	p.Arg253Pro	missense	N/A	ENSP00000362401.3	Q9Y271
	CYSLTR1	ENST00000614798.1	TSL:1	c.758_759delGTinsCC	p.Arg253Pro	missense	N/A	ENSP00000478492.1	Q9Y271
	CYSLTR1	ENST00000856868.1		c.758_759delGTinsCC	p.Arg253Pro	missense	N/A	ENSP00000526927.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-77528485;