13-48706918-A-C

Variant names:

• chr13-48706918-A-C
• NM_001308476.3:c.101A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308476.3(CYSLTR2):​c.101A>C​(p.Glu34Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CYSLTR2 NM_001308476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27
• Publications: 0 publications found

Genes affected

CYSLTR2 (HGNC:18274): (cysteinyl leukotriene receptor 2) The cysteinyl leukotrienes LTC4, LTD4, and LTE4 are important mediators of human bronchial asthma. Pharmacologic studies have determined that cysteinyl leukotrienes activate at least 2 receptors, the protein encoded by this gene and CYSLTR1. This encoded receptor is a member of the superfamily of G protein-coupled receptors. It seems to play a major role in endocrine and cardiovascular systems. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15046862).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR2	NM_001308476.3	MANE Select	c.101A>C	p.Glu34Ala	missense	Exon 5 of 5	NP_001295405.1	Q9NS75
	CYSLTR2	NM_001308465.3		c.101A>C	p.Glu34Ala	missense	Exon 6 of 6	NP_001295394.1	Q9NS75
	CYSLTR2	NM_001308467.3		c.101A>C	p.Glu34Ala	missense	Exon 6 of 6	NP_001295396.1	Q9NS75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR2	ENST00000682523.1	MANE Select	c.101A>C	p.Glu34Ala	missense	Exon 5 of 5	ENSP00000508181.1	Q9NS75
	CYSLTR2	ENST00000614739.4	TSL:1	c.101A>C	p.Glu34Ala	missense	Exon 5 of 5	ENSP00000477930.1	Q9NS75
	CYSLTR2	ENST00000282018.4	TSL:6	c.101A>C	p.Glu34Ala	missense	Exon 1 of 1	ENSP00000282018.3	Q9NS75

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.3
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.058	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.48		Gain of catalytic residue at R29 (P = 8e-04)
MVP		0.45
MPC		0.13
ClinPred		0.57	D
GERP RS		3.6
PromoterAI		-0.0031	Neutral
Varity_R		0.13
gMVP		0.12
Mutation Taster		=95/5	polymorphism

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

hg19: chr13-49281054;