chrX-78272743-C-T

Variant names:

• chrX-78272743-C-T
• rs1474571793
• NM_006639.4:c.1004G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006639.4(CYSLTR1):​c.1004G>A​(p.Cys335Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,080,242 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000019 (0 hom. 9 hem.)
  • Failed GnomAD Quality Control
• Consequence: CYSLTR1 NM_006639.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0100
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07071149).
• BS2: High Hemizygotes in GnomAdExome4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006639.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR1	NM_006639.4	MANE Select	c.1004G>A	p.Cys335Tyr	missense	Exon 3 of 3	NP_006630.1	Q9Y271
	CYSLTR1	NM_001282186.2		c.1004G>A	p.Cys335Tyr	missense	Exon 2 of 2	NP_001269115.1	Q9Y271
	CYSLTR1	NM_001282187.2		c.1004G>A	p.Cys335Tyr	missense	Exon 4 of 4	NP_001269116.1	Q9Y271

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR1	ENST00000373304.4	TSL:1 MANE Select	c.1004G>A	p.Cys335Tyr	missense	Exon 3 of 3	ENSP00000362401.3	Q9Y271
	CYSLTR1	ENST00000614798.1	TSL:1	c.1004G>A	p.Cys335Tyr	missense	Exon 2 of 2	ENSP00000478492.1	Q9Y271
	CYSLTR1	ENST00000856868.1		c.1004G>A	p.Cys335Tyr	missense	Exon 4 of 4	ENSP00000526927.1

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111714 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000277

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

GnomAD4 exome AF: 0.0000194 AC: 21 AN: 1080242 Hom.: 0 Cov.: 28 AF XY: 0.0000257 AC XY: 9 AN XY: 350336

African (AFR) AF: 0.00 AC: 0 AN: 25757

American (AMR) AF: 0.00 AC: 0 AN: 32897

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18351

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30042

South Asian (SAS) AF: 0.00 AC: 0 AN: 50266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4032

European-Non Finnish (NFE) AF: 0.0000228 AC: 19 AN: 833715

Other (OTH) AF: 0.0000221 AC: 1 AN: 45278

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000895 AC: 1 AN: 111714 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33926

African (AFR) AF: 0.00 AC: 0 AN: 30770

American (AMR) AF: 0.00 AC: 0 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.000277 AC: 1 AN: 3608

South Asian (SAS) AF: 0.00 AC: 0 AN: 2714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5965

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53177

Other (OTH) AF: 0.00 AC: 0 AN: 1500

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.034
DANN	Benign	0.27
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.010
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.063
Sift	Benign	0.32	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.30		Loss of methylation at K336 (P = 0.0226)
MVP		0.72
MPC		0.0073
ClinPred		0.043	T
GERP RS		0.18
Varity_R		0.072
gMVP		0.29
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1474571793; hg19: chrX-77528240;