Variant chrX-78273584-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006639.4(CYSLTR1):c.163A>C(p.Lys55Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,209,660 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 58 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 57 hem. )

Consequence

CYSLTR1
NM_006639.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2914912).

BS2

High Hemizygotes in GnomAdExome4 at 57 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	3/3	ENST00000373304.4	NP_006630.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282186.2 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	2/2		NP_001269115.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282187.2 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	4/4		NP_001269116.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282188.2 linkuse as main transcript	c.163A>C	p.Lys55Gln	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.163A>C	p.Lys55Gln	missense_variant	3/3	1	NM_006639.4	ENSP00000362401.3		Q9Y271
CYSLTR1	ENST00000614798.1 linkuse as main transcript	c.163A>C	p.Lys55Gln	missense_variant	2/2	1		ENSP00000478492.1		Q9Y271

Frequencies

GnomAD3 genomes

AF:

0.0000359

AC:

AN:

111493

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33703

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000753

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

182932

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.0000736

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

142

AN:

1098167

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

363549

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000359

AC:

AN:

111493

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33703

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000753

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Sep 03, 2024

The c.163A>C (p.K55Q) alteration is located in exon 3 (coding exon 1) of the CYSLTR1 gene. This alteration results from a A to C substitution at nucleotide position 163, causing the lysine (K) at amino acid position 55 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;T

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.82

N;.

REVEL

Benign

0.11

Sift

Benign

0.15

T;.

Sift4G

Benign

0.22

T;T

Polyphen

0.92

P;P

Vest4

0.23

MVP

0.71

MPC

0.034

ClinPred

0.18

GERP RS

4.5

Varity_R

0.50

gMVP

0.31

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