rs320995

Positions:

• chrX-78272820-G-A
• chrX-78272820-G-C
• chrX-78272820-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_006639.4(CYSLTR1):​c.927C>T​(p.Phe309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.73 (21100 hom., 22994 hem., cov: 22)
  • Exomes 𝑓: 0.77 (222867 hom. 279930 hem.)
  • Failed GnomAD Quality Control
• Consequence: CYSLTR1 NM_006639.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant X-78272820-G-A is Benign according to our data. Variant chrX-78272820-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.281 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.927C>T	p.Phe309=	synonymous_variant	3/3	ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.927C>T	p.Phe309=	synonymous_variant	2/2		NP_001269115.1
CYSLTR1	NM_001282187.2	c.927C>T	p.Phe309=	synonymous_variant	4/4		NP_001269116.1
CYSLTR1	NM_001282188.2	c.927C>T	p.Phe309=	synonymous_variant	4/4		NP_001269117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4	c.927C>T	p.Phe309=	synonymous_variant	3/3	1	NM_006639.4	ENSP00000362401	P1
CYSLTR1	ENST00000614798.1	c.927C>T	p.Phe309=	synonymous_variant	2/2	1		ENSP00000478492	P1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 79935 AN: 109623 Hom.: 21110 Cov.: 22 AF XY: 0.720 AC XY: 22957 AN XY: 31897

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.731

GnomAD3 exomes AF: 0.732 AC: 133376 AN: 182325 Hom.: 31264 AF XY: 0.731 AC XY: 49020 AN XY: 67015

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.648

Gnomad ASJ exome AF: 0.832

Gnomad EAS exome AF: 0.631

Gnomad SAS exome AF: 0.641

Gnomad FIN exome AF: 0.788

Gnomad NFE exome AF: 0.788

Gnomad OTH exome AF: 0.760

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.775 AC: 850271 AN: 1097657 Hom.: 222867 Cov.: 44 AF XY: 0.771 AC XY: 279930 AN XY: 363095

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.647

Gnomad4 ASJ exome AF: 0.830

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.791

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.729 AC: 79955 AN: 109678 Hom.: 21100 Cov.: 22 AF XY: 0.719 AC XY: 22994 AN XY: 31962

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.728

Alfa AF: 0.771 Hom.: 59943

Bravo AF: 0.719

EpiCase AF: 0.787

EpiControl AF: 0.787

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.8
DANN	Benign	0.51

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: rs320995; hg19: chrX-77528317;