chrX-78327870-G-A

Variant names:

• chrX-78327870-G-A
• rs7066737
• ENST00000614798.1:c.-593C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000614798.1(CYSLTR1):​c.-593C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 111,110 control chromosomes in the GnomAD database, including 1,518 homozygotes. There are 3,569 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 0.12 (1518 hom., 3569 hem., cov: 22)
• Consequence: CYSLTR1 ENST00000614798.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000614798.1	c.-593C>T		upstream_gene_variant		1		ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 12841 AN: 111058 Hom.: 1517 Cov.: 22

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0212

Gnomad EAS AF: 0.000564

Gnomad SAS AF: 0.0254

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0910

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

GnomAD4 genome AF: 0.116 AC: 12850 AN: 111110 Hom.: 1518 Cov.: 22 AF XY: 0.107 AC XY: 3569 AN XY: 33366

African (AFR) AF: 0.363 AC: 10986 AN: 30277

American (AMR) AF: 0.0559 AC: 590 AN: 10550

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 56 AN: 2647

East Asian (EAS) AF: 0.000566 AC: 2 AN: 3533

South Asian (SAS) AF: 0.0255 AC: 67 AN: 2630

European-Finnish (FIN) AF: 0.0311 AC: 186 AN: 5974

Middle Eastern (MID) AF: 0.0833 AC: 18 AN: 216

European-Non Finnish (NFE) AF: 0.0151 AC: 802 AN: 53098

Other (OTH) AF: 0.0892 AC: 134 AN: 1502

Alfa AF: 0.170 Hom.: 3091

Bravo AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.56
PhyloP100		0.60
PromoterAI		-0.12	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7066737; hg19: chrX-77583367;