Variant X-78273457-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_006639.4(CYSLTR1):c.290G>A(p.Arg97His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,209,577 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000040 ( 0 hom. 17 hem. )

Consequence

CYSLTR1
NM_006639.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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 Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.881

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYSLTR1	NM_006639.4 linkuse as main transcript	c.290G>A	p.Arg97His	missense_variant	3/3	ENST00000373304.4
CYSLTR1	NM_001282186.2 linkuse as main transcript	c.290G>A	p.Arg97His	missense_variant	2/2
CYSLTR1	NM_001282187.2 linkuse as main transcript	c.290G>A	p.Arg97His	missense_variant	4/4
CYSLTR1	NM_001282188.2 linkuse as main transcript	c.290G>A	p.Arg97His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYSLTR1	ENST00000373304.4 linkuse as main transcript	c.290G>A	p.Arg97His	missense_variant	3/3	1	NM_006639.4	P1
CYSLTR1	ENST00000614798.1 linkuse as main transcript	c.290G>A	p.Arg97His	missense_variant	2/2	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111791

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

33997

show subpopulations

Gnomad AFR

AF:

0.0000650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000954

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000548

AC:

AN:

182330

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

66972

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000739

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1097786

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

363202

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000663

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000404

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111791

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

33997

show subpopulations

Gnomad4 AFR

AF:

0.0000650

Gnomad4 AMR

AF:

0.0000954

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000742

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

D;D

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.064

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-4.5

D;.

REVEL

Pathogenic

0.82

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.049

D;D

Polyphen

1.0

D;D

Vest4

0.89

MutPred

0.75

Loss of methylation at R97 (P = 0.0298);Loss of methylation at R97 (P = 0.0298);

MVP

0.94

MPC

0.046

ClinPred

0.77

GERP RS

4.5

Varity_R

0.86

gMVP

0.43

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over