rs320996

Positions:

• chrX-78271975-A-C
• chrX-78271975-A-G
• chrX-78271975-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006639.4(CYSLTR1):​c.*758T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 110,354 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 79 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 0.0018 (0 hom., 79 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CYSLTR1 NM_006639.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Hemizygotes in GnomAd4 at 79 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.*758T>G		3_prime_UTR_variant	3/3	ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.*758T>G		3_prime_UTR_variant	2/2		NP_001269115.1
CYSLTR1	NM_001282187.2	c.*758T>G		3_prime_UTR_variant	4/4		NP_001269116.1
CYSLTR1	NM_001282188.2	c.*758T>G		3_prime_UTR_variant	4/4		NP_001269117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304	c.*758T>G		3_prime_UTR_variant	3/3	1	NM_006639.4	ENSP00000362401.3
CYSLTR1	ENST00000614798	c.*758T>G		3_prime_UTR_variant	2/2	1		ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 199 AN: 110301 Hom.: 0 Cov.: 22 AF XY: 0.00243 AC XY: 79 AN XY: 32553

Gnomad AFR AF: 0.000164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00202

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00180 AC: 199 AN: 110354 Hom.: 0 Cov.: 22 AF XY: 0.00242 AC XY: 79 AN XY: 32616

Gnomad4 AFR AF: 0.000164

Gnomad4 AMR AF: 0.000294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00200

Alfa AF: 0.000110 Hom.: 52318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.37

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: rs320996; hg19: chrX-77527472;