rs762291403

Variant names:

• chrX-78273260-G-C
• rs762291403
• NM_006639.4:c.487C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-78273260-G-C
• chrX-78273260-G-T

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.487C>G​(p.Pro163Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,207,889 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000024 (0 hom. 8 hem.)
• Consequence: CYSLTR1 NM_006639.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0150
• Publications: 1 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=0.0718666).
• BS2: High Hemizygotes in GnomAdExome4 at 8 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.487C>G	p.Pro163Ala	missense	Exon 3 of 3	NP_006630.1	Q9Y271
	CYSLTR1	NM_001282186.2		c.487C>G	p.Pro163Ala	missense	Exon 2 of 2	NP_001269115.1	Q9Y271
	CYSLTR1	NM_001282187.2		c.487C>G	p.Pro163Ala	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.487C>G	p.Pro163Ala	missense	Exon 3 of 3	ENSP00000362401.3	Q9Y271
	CYSLTR1	ENST00000614798.1	TSL:1	c.487C>G	p.Pro163Ala	missense	Exon 2 of 2	ENSP00000478492.1	Q9Y271
	CYSLTR1	ENST00000856868.1		c.487C>G	p.Pro163Ala	missense	Exon 4 of 4	ENSP00000526927.1

Frequencies

GnomAD3 genomes AF: 0.00000899 AC: 1 AN: 111247 Hom.: 0 Cov.: 22

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 180600 AF XY: 0.0000305

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000248

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000237 AC: 26 AN: 1096589 Hom.: 0 Cov.: 33 AF XY: 0.0000221 AC XY: 8 AN XY: 362131

African (AFR) AF: 0.00 AC: 0 AN: 26342

American (AMR) AF: 0.00 AC: 0 AN: 35002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19335

East Asian (EAS) AF: 0.00 AC: 0 AN: 30173

South Asian (SAS) AF: 0.00 AC: 0 AN: 53820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.0000309 AC: 26 AN: 841281

Other (OTH) AF: 0.00 AC: 0 AN: 46026

GnomAD4 genome AF: 0.00000898 AC: 1 AN: 111300 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33520

African (AFR) AF: 0.00 AC: 0 AN: 30640

American (AMR) AF: 0.00 AC: 0 AN: 10358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.00 AC: 0 AN: 2651

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5907

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53098

Other (OTH) AF: 0.00 AC: 0 AN: 1527

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.015
DANN	Benign	0.24
DEOGEN2	Benign	0.091	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.095	N
PhyloP100		-0.015
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.029
Sift	Benign	0.44	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.077
MutPred		0.33		Loss of methylation at K168 (P = 0.0613)
MVP		0.89
MPC		0.0081
ClinPred		0.020	T
GERP RS		-5.9
Varity_R		0.023
gMVP		0.074
Mutation Taster		=94/6	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: rs762291403; hg19: chrX-77528757;