X-78271975-A-G

Position:

• chrX-78271975-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006639.4(CYSLTR1):​c.*758T>C variant causes a 3 prime UTR 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 0.72 (20769 hom., 23190 hem., cov: 22)
  • Exomes 𝑓: 1.0 (0 hom. 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.*758T>C		3_prime_UTR_variant	3/3	ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.*758T>C		3_prime_UTR_variant	2/2		NP_001269115.1
CYSLTR1	NM_001282187.2	c.*758T>C		3_prime_UTR_variant	4/4		NP_001269116.1
CYSLTR1	NM_001282188.2	c.*758T>C		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>C		3_prime_UTR_variant	3/3	1	NM_006639.4	ENSP00000362401.3
CYSLTR1	ENST00000614798	c.*758T>C		3_prime_UTR_variant	2/2	1		ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79640 AN: 110261 Hom.: 20777 Cov.: 22 AF XY: 0.712 AC XY: 23154 AN XY: 32535

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 1.00 AC: 1 AN: 1 Hom.: 0 Cov.: 0 AF XY: 1.00 AC XY: 1 AN XY: 1

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.722 AC: 79661 AN: 110314 Hom.: 20769 Cov.: 22 AF XY: 0.711 AC XY: 23190 AN XY: 32598

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.722

Alfa AF: 0.766 Hom.: 52318

Bravo AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.35

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;