chrX-78273386-G-A

Position:

chrX-78273386-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2

The NM_006639.4(CYSLTR1):c.361C>T(p.Arg121Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,209,248 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000022 ( 0 hom. 11 hem. )

Consequence

CYSLTR1
NM_006639.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.896

BP6

Variant X-78273386-G-A is Benign according to our data. Variant chrX-78273386-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2660971.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4 link	c.361C>T	p.Arg121Trp	missense_variant	3/3	ENST00000373304.4	NP_006630.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282186.2 link	c.361C>T	p.Arg121Trp	missense_variant	2/2		NP_001269115.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282187.2 link	c.361C>T	p.Arg121Trp	missense_variant	4/4		NP_001269116.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282188.2 link	c.361C>T	p.Arg121Trp	missense_variant	4/4		NP_001269117.1	Q9Y271Q38Q91Q38Q88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4 link	c.361C>T	p.Arg121Trp	missense_variant	3/3	1	NM_006639.4	ENSP00000362401.3		Q9Y271
CYSLTR1	ENST00000614798.1 link	c.361C>T	p.Arg121Trp	missense_variant	2/2	1		ENSP00000478492.1		Q9Y271

Frequencies

GnomAD3 genomes

AF:

0.0000539

AC:

AN:

111322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33556

show subpopulations

Gnomad AFR

AF:

0.0000327

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:

0.0000942

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000328

AC:

AN:

182788

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

67338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000526

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000491

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1097926

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363312

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000226

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000539

AC:

AN:

111322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33556

show subpopulations

Gnomad4 AFR

AF:

0.0000327

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:

0.0000942

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.361C>T (p.R121W) alteration is located in exon 3 (coding exon 1) of the CYSLTR1 gene. This alteration results from a C to T substitution at nucleotide position 361, causing the arginine (R) at amino acid position 121 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

CYSLTR1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.69

BayesDel_noAF

Pathogenic

0.76

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;D

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

.;D

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.3

H;H

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-7.9

D;.

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.55

MutPred

0.82

Gain of catalytic residue at S118 (P = 0.2446);Gain of catalytic residue at S118 (P = 0.2446);

MVP

1.0

MPC

0.048

ClinPred

0.99

GERP RS

3.6

Varity_R

0.98

gMVP

0.90

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