X-78277128-C-T

Variant names:

• chrX-78277128-C-T
• rs320991
• NM_006639.4:c.-27-3355G>A

Variant summary

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

The NM_006639.4(CYSLTR1):​c.-27-3355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 110,007 control chromosomes in the GnomAD database, including 13,902 homozygotes. There are 17,424 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 0.55 (13902 hom., 17424 hem., cov: 21)
• Consequence: CYSLTR1 NM_006639.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.-27-3355G>A		intron_variant	Intron 2 of 2	ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.-27-3355G>A		intron_variant	Intron 1 of 1		NP_001269115.1
CYSLTR1	NM_001282187.2	c.-27-3355G>A		intron_variant	Intron 3 of 3		NP_001269116.1
CYSLTR1	NM_001282188.2	c.-27-3355G>A		intron_variant	Intron 3 of 3		NP_001269117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4	c.-27-3355G>A		intron_variant	Intron 2 of 2	1	NM_006639.4	ENSP00000362401.3
CYSLTR1	ENST00000614798.1	c.-27-3355G>A		intron_variant	Intron 1 of 1	1		ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 60240 AN: 109954 Hom.: 13915 Cov.: 21

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.548 AC: 60239 AN: 110007 Hom.: 13902 Cov.: 21 AF XY: 0.539 AC XY: 17424 AN XY: 32297

African (AFR) AF: 0.201 AC: 6106 AN: 30396

American (AMR) AF: 0.534 AC: 5519 AN: 10330

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 1987 AN: 2611

East Asian (EAS) AF: 0.520 AC: 1795 AN: 3454

South Asian (SAS) AF: 0.533 AC: 1362 AN: 2555

European-Finnish (FIN) AF: 0.698 AC: 3973 AN: 5688

Middle Eastern (MID) AF: 0.592 AC: 129 AN: 218

European-Non Finnish (NFE) AF: 0.724 AC: 38066 AN: 52573

Other (OTH) AF: 0.572 AC: 868 AN: 1517

Alfa AF: 0.639 Hom.: 42712

Bravo AF: 0.526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.91
PhyloP100		-0.65
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: rs320991; hg19: chrX-77532625;