X-78273602-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006639.4(CYSLTR1):​c.145A>G​(p.Ile49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Consequence

CYSLTR1
NM_006639.4 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17634481).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYSLTR1NM_006639.4 linkuse as main transcriptc.145A>G p.Ile49Val missense_variant 3/3 ENST00000373304.4 NP_006630.1 Q9Y271Q38Q91Q38Q88
CYSLTR1NM_001282186.2 linkuse as main transcriptc.145A>G p.Ile49Val missense_variant 2/2 NP_001269115.1 Q9Y271Q38Q91Q38Q88
CYSLTR1NM_001282187.2 linkuse as main transcriptc.145A>G p.Ile49Val missense_variant 4/4 NP_001269116.1 Q9Y271Q38Q91Q38Q88
CYSLTR1NM_001282188.2 linkuse as main transcriptc.145A>G p.Ile49Val missense_variant 4/4 NP_001269117.1 Q9Y271Q38Q91Q38Q88

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYSLTR1ENST00000373304.4 linkuse as main transcriptc.145A>G p.Ile49Val missense_variant 3/31 NM_006639.4 ENSP00000362401.3 Q9Y271
CYSLTR1ENST00000614798.1 linkuse as main transcriptc.145A>G p.Ile49Val missense_variant 2/21 ENSP00000478492.1 Q9Y271

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 22, 2024The c.145A>G (p.I49V) alteration is located in exon 3 (coding exon 1) of the CYSLTR1 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the isoleucine (I) at amino acid position 49 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
15
DANN
Benign
0.96
DEOGEN2
Benign
0.13
T;T
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.56
.;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.58
N;.
REVEL
Benign
0.026
Sift
Benign
0.088
T;.
Sift4G
Benign
0.65
T;T
Polyphen
0.0040
B;B
Vest4
0.091
MutPred
0.66
Loss of stability (P = 0.1061);Loss of stability (P = 0.1061);
MVP
0.89
MPC
0.0085
ClinPred
0.099
T
GERP RS
1.9
Varity_R
0.090
gMVP
0.062

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-77529099; API