rs321006

Positions:

• chrX-78314112-G-A
• chrX-78314112-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006639.4(CYSLTR1):​c.-115+13193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 110,704 control chromosomes in the GnomAD database, including 677 homozygotes. There are 3,421 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 0.11 (677 hom., 3421 hem., cov: 22)
• Consequence: CYSLTR1 NM_006639.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.-115+13193C>T		intron_variant		ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.-28+13193C>T		intron_variant			NP_001269115.1
CYSLTR1	NM_001282187.2	c.-115+823C>T		intron_variant			NP_001269116.1
CYSLTR1	NM_001282188.2	c.-115+4498C>T		intron_variant			NP_001269117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4	c.-115+13193C>T		intron_variant		1	NM_006639.4	ENSP00000362401.3
CYSLTR1	ENST00000614798.1	c.-28+13193C>T		intron_variant		1		ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 11784 AN: 110652 Hom.: 680 Cov.: 22 AF XY: 0.104 AC XY: 3421 AN XY: 32882

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.126

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.0841

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 11768 AN: 110704 Hom.: 677 Cov.: 22 AF XY: 0.104 AC XY: 3421 AN XY: 32944

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0507

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0569

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.0831

Alfa AF: 0.138 Hom.: 6799

Bravo AF: 0.0904

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs321006; hg19: chrX-77569609;