Variant chrX-78273511-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006639.4(CYSLTR1):c.236G>T(p.Arg79Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 22)

Failed GnomAD Quality Control

Consequence

CYSLTR1
NM_006639.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69

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]

CYSLTR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4 linkuse as main transcript	c.236G>T	p.Arg79Leu	missense_variant	3/3	ENST00000373304.4	NP_006630.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282186.2 linkuse as main transcript	c.236G>T	p.Arg79Leu	missense_variant	2/2		NP_001269115.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282187.2 linkuse as main transcript	c.236G>T	p.Arg79Leu	missense_variant	4/4		NP_001269116.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282188.2 linkuse as main transcript	c.236G>T	p.Arg79Leu	missense_variant	4/4		NP_001269117.1	Q9Y271Q38Q91Q38Q88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4 linkuse as main transcript	c.236G>T	p.Arg79Leu	missense_variant	3/3	1	NM_006639.4	ENSP00000362401.3		Q9Y271
CYSLTR1	ENST00000614798.1 linkuse as main transcript	c.236G>T	p.Arg79Leu	missense_variant	2/2	1		ENSP00000478492.1		Q9Y271

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111882

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34074

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182858

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67426

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000894

AC:

AN:

111882

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34074

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

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 submitter

clinical testing

Ambry Genetics

Apr 17, 2023

The c.236G>T (p.R79L) alteration is located in exon 3 (coding exon 1) of the CYSLTR1 gene. This alteration results from a G to T substitution at nucleotide position 236, causing the arginine (R) at amino acid position 79 to be replaced by a leucine (L). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

D;D

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

.;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.7

L;L

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.2

D;.

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.43

T;T

Polyphen

1.0

D;D

Vest4

0.87

MVP

0.98

MPC

0.046

ClinPred

0.97

GERP RS

4.5

Varity_R

0.96

gMVP

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over