rs321007

Variant names:

• chrX-78313715-G-A
• rs321007
• NM_006639.4:c.-115+13590C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-78313715-G-A
• chrX-78313715-G-T

Variant summary

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

The NM_006639.4(CYSLTR1):​c.-115+13590C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 109,926 control chromosomes in the GnomAD database, including 12,679 homozygotes. There are 16,156 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 0.51 (12679 hom., 16156 hem., cov: 22)
• Consequence: CYSLTR1 NM_006639.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.-115+13590C>T		intron_variant	Intron 1 of 2	ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.-28+13590C>T		intron_variant	Intron 1 of 1		NP_001269115.1
CYSLTR1	NM_001282187.2	c.-115+1220C>T		intron_variant	Intron 2 of 3		NP_001269116.1
CYSLTR1	NM_001282188.2	c.-115+4895C>T		intron_variant	Intron 2 of 3		NP_001269117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4	c.-115+13590C>T		intron_variant	Intron 1 of 2	1	NM_006639.4	ENSP00000362401.3
CYSLTR1	ENST00000614798.1	c.-28+13590C>T		intron_variant	Intron 1 of 1	1		ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 56047 AN: 109876 Hom.: 12691 Cov.: 22

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.510 AC: 56033 AN: 109926 Hom.: 12679 Cov.: 22 AF XY: 0.502 AC XY: 16156 AN XY: 32208

African (AFR) AF: 0.135 AC: 4101 AN: 30420

American (AMR) AF: 0.517 AC: 5320 AN: 10285

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 1922 AN: 2620

East Asian (EAS) AF: 0.490 AC: 1685 AN: 3441

South Asian (SAS) AF: 0.517 AC: 1323 AN: 2560

European-Finnish (FIN) AF: 0.661 AC: 3745 AN: 5664

Middle Eastern (MID) AF: 0.600 AC: 129 AN: 215

European-Non Finnish (NFE) AF: 0.696 AC: 36590 AN: 52564

Other (OTH) AF: 0.530 AC: 785 AN: 1482

Alfa AF: 0.630 Hom.: 36805

Bravo AF: 0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs321007; hg19: chrX-77569212;