rs912277

Positions:

• chr13-48709515-A-G
• chr13-48709515-A-T

Variant summary

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

The NM_001308476.3(CYSLTR2):​c.*1657A>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 0.0618 in 154,280 control chromosomes in the GnomAD database, including 388 homozygotes. 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 0.062 (384 hom., cov: 32)
  • Exomes 𝑓: 0.065 (4 hom.)
• Consequence: CYSLTR2 NM_001308476.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR2	NM_001308476.3	c.*1657A>G		3_prime_UTR_variant	5/5	ENST00000682523.1	NP_001295405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR2	ENST00000682523.1	c.*1657A>G		3_prime_UTR_variant	5/5		NM_001308476.3	ENSP00000508181.1
CYSLTR2	ENST00000282018.4	c.*1657A>G		3_prime_UTR_variant	1/1	6		ENSP00000282018.3

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9400 AN: 152104 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0651 AC: 134 AN: 2058 Hom.: 4 Cov.: 0 AF XY: 0.0680 AC XY: 69 AN XY: 1014

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0645

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0618 AC: 9407 AN: 152222 Hom.: 384 Cov.: 32 AF XY: 0.0643 AC XY: 4787 AN XY: 74420

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.0388

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0390 Hom.: 45

Bravo AF: 0.0614

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.67

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: rs912277; hg19: chr13-49283651;