chr13-48654621-T-C

Position:

• chr13-48654621-T-C

Variant summary

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

The NM_001308476.3(CYSLTR2):​c.-266+604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 152,214 control chromosomes in the GnomAD database, including 659 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 0.078 (659 hom., cov: 32)
• Consequence: CYSLTR2 NM_001308476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR2	NM_001308476.3	c.-266+604T>C		intron_variant		ENST00000682523.1	NP_001295405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR2	ENST00000682523.1	c.-266+604T>C		intron_variant			NM_001308476.3	ENSP00000508181.1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11805 AN: 152098 Hom.: 660 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0775 AC: 11798 AN: 152214 Hom.: 659 Cov.: 32 AF XY: 0.0740 AC XY: 5507 AN XY: 74418

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0449

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.102 Hom.: 216

Bravo AF: 0.0733

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.79
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11617224; hg19: chr13-49228757;