chrX-78273698-T-G

Position:

chrX-78273698-T-G

Variant summary

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

The NM_006639.4(CYSLTR1):c.49A>C(p.Thr17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,204,309 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 4 hem. )

Consequence

CYSLTR1
NM_006639.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27115303).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4 linkuse as main transcript	c.49A>C	p.Thr17Pro	missense_variant	3/3	ENST00000373304.4	NP_006630.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282186.2 linkuse as main transcript	c.49A>C	p.Thr17Pro	missense_variant	2/2		NP_001269115.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282187.2 linkuse as main transcript	c.49A>C	p.Thr17Pro	missense_variant	4/4		NP_001269116.1	Q9Y271Q38Q91Q38Q88
CYSLTR1	NM_001282188.2 linkuse as main transcript	c.49A>C	p.Thr17Pro	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.49A>C	p.Thr17Pro	missense_variant	3/3	1	NM_006639.4	ENSP00000362401.3		Q9Y271
CYSLTR1	ENST00000614798.1 linkuse as main transcript	c.49A>C	p.Thr17Pro	missense_variant	2/2	1		ENSP00000478492.1		Q9Y271

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112155

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34313

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000552

AC:

AN:

181149

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

66001

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1092154

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

358042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000167

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112155

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34313

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:

0.0000564

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

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

Dec 08, 2023

The c.49A>C (p.T17P) 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 49, causing the threonine (T) at amino acid position 17 to be replaced by a proline (P). 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

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

T;T

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.52

.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.14

Sift

Uncertain

0.0070

D;.

Sift4G

Benign

0.16

T;T

Polyphen

0.80

P;P

Vest4

0.20

MutPred

0.36

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);

MVP

0.92

MPC

0.010

ClinPred

0.30

GERP RS

4.5

Varity_R

0.61

gMVP

0.27

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