rs320995

Variant names:

• chrX-78272820-G-A
• rs320995
• NM_006639.4:c.927C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_006639.4(CYSLTR1):​c.927C>T​(p.Phe309Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.73 (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
• Publications: 45 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.281 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.927C>T	p.Phe309Phe	synonymous_variant	Exon 3 of 3	ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.927C>T	p.Phe309Phe	synonymous_variant	Exon 2 of 2		NP_001269115.1
CYSLTR1	NM_001282187.2	c.927C>T	p.Phe309Phe	synonymous_variant	Exon 4 of 4		NP_001269116.1
CYSLTR1	NM_001282188.2	c.927C>T	p.Phe309Phe	synonymous_variant	Exon 4 of 4		NP_001269117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4	c.927C>T	p.Phe309Phe	synonymous_variant	Exon 3 of 3	1	NM_006639.4	ENSP00000362401.3
CYSLTR1	ENST00000614798.1	c.927C>T	p.Phe309Phe	synonymous_variant	Exon 2 of 2	1		ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 79935 AN: 109623 Hom.: 21110 Cov.: 22

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

GnomAD2 exomes AF: 0.732 AC: 133376 AN: 182325 AF XY: 0.731

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 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

African (AFR) AF: 0.651 AC: 17177 AN: 26391

American (AMR) AF: 0.647 AC: 22722 AN: 35112

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 16083 AN: 19371

East Asian (EAS) AF: 0.592 AC: 17886 AN: 30189

South Asian (SAS) AF: 0.637 AC: 34477 AN: 54088

European-Finnish (FIN) AF: 0.791 AC: 32047 AN: 40497

Middle Eastern (MID) AF: 0.733 AC: 3028 AN: 4132

European-Non Finnish (NFE) AF: 0.798 AC: 671513 AN: 841808

Other (OTH) AF: 0.767 AC: 35338 AN: 46069

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

African (AFR) AF: 0.653 AC: 19729 AN: 30210

American (AMR) AF: 0.657 AC: 6662 AN: 10144

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2217 AN: 2621

East Asian (EAS) AF: 0.612 AC: 2135 AN: 3487

South Asian (SAS) AF: 0.631 AC: 1609 AN: 2551

European-Finnish (FIN) AF: 0.789 AC: 4463 AN: 5657

Middle Eastern (MID) AF: 0.736 AC: 159 AN: 216

European-Non Finnish (NFE) AF: 0.788 AC: 41455 AN: 52638

Other (OTH) AF: 0.728 AC: 1082 AN: 1487

Alfa AF: 0.764 Hom.: 83170

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
PhyloP100		0.28
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: rs320995; hg19: chrX-77528317; COSMIC: COSV108218544;