X-78271975-A-G

Variant names:

• chrX-78271975-A-G
• rs320996
• NM_006639.4:c.*758T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.92).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 1 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006639.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR1	NM_006639.4	MANE Select	c.*758T>C		3_prime_UTR	Exon 3 of 3	NP_006630.1
	CYSLTR1	NM_001282186.2		c.*758T>C		3_prime_UTR	Exon 2 of 2	NP_001269115.1
	CYSLTR1	NM_001282187.2		c.*758T>C		3_prime_UTR	Exon 4 of 4	NP_001269116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR1	ENST00000373304.4	TSL:1 MANE Select	c.*758T>C		3_prime_UTR	Exon 3 of 3	ENSP00000362401.3
	CYSLTR1	ENST00000614798.1	TSL:1	c.*758T>C		3_prime_UTR	Exon 2 of 2	ENSP00000478492.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79640 AN: 110261 Hom.: 20777 Cov.: 22

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 1 AN: 1

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.639 AC: 19446 AN: 30450

American (AMR) AF: 0.654 AC: 6663 AN: 10191

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2226 AN: 2639

East Asian (EAS) AF: 0.611 AC: 2144 AN: 3507

South Asian (SAS) AF: 0.627 AC: 1635 AN: 2609

European-Finnish (FIN) AF: 0.768 AC: 4425 AN: 5765

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

European-Non Finnish (NFE) AF: 0.785 AC: 41434 AN: 52765

Other (OTH) AF: 0.722 AC: 1083 AN: 1501

Alfa AF: 0.765 Hom.: 79573

Bravo AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.35
PhyloP100		-0.098
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: rs320996; hg19: chrX-77527472;