13-48709515-A-G

Variant names:

• chr13-48709515-A-G
• rs912277
• NM_001308476.3:c.*1657A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYSLTR2	NM_001308476.3	c.*1657A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000682523.1	NP_001295405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYSLTR2	ENST00000682523.1	c.*1657A>G		3_prime_UTR_variant	Exon 5 of 5		NM_001308476.3	ENSP00000508181.1
CYSLTR2	ENST00000282018.4	c.*1657A>G		3_prime_UTR_variant	Exon 1 of 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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0645 AC: 130 AN: 2016

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.136 AC: 3 AN: 22

Other (OTH) AF: 0.00 AC: 0 AN: 12

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

African (AFR) AF: 0.0439 AC: 1824 AN: 41550

American (AMR) AF: 0.108 AC: 1651 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.0388 AC: 201 AN: 5186

South Asian (SAS) AF: 0.106 AC: 509 AN: 4814

European-Finnish (FIN) AF: 0.0807 AC: 856 AN: 10602

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0583 AC: 3965 AN: 67994

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0492 Hom.: 101

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
PhyloP100		0.84

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: rs912277; hg19: chr13-49283651;