Variant chr13-48706965-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001308476.3(CYSLTR2):c.148T>G(p.Phe50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,614,178 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 45 hom. )

Consequence

CYSLTR2
NM_001308476.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.256

Variant links:

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]

CYSLTR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027964711).

BP6

Variant 13-48706965-T-G is Benign according to our data. Variant chr13-48706965-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 769848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR2	NM_001308476.3 linkuse as main transcript	c.148T>G	p.Phe50Val	missense_variant	5/5	ENST00000682523.1	NP_001295405.1	Q9NS75Q5KU17A4ZKH2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYSLTR2	ENST00000682523.1 linkuse as main transcript	c.148T>G	p.Phe50Val	missense_variant	5/5		NM_001308476.3	ENSP00000508181.1	Q9NS75
CYSLTR2	ENST00000614739.4 linkuse as main transcript	c.148T>G	p.Phe50Val	missense_variant	5/5	1		ENSP00000477930.1	Q9NS75
CYSLTR2	ENST00000282018.4 linkuse as main transcript	c.148T>G	p.Phe50Val	missense_variant	1/1	6		ENSP00000282018.3	Q9NS75

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

670

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00616

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00486

AC:

1220

AN:

251262

Hom.:

AF XY:

0.00495

AC XY:

672

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00564

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00559

Gnomad NFE exome

AF:

0.00637

Gnomad OTH exome

AF:

0.00865

GnomAD4 exome

AF:

0.00635

AC:

9276

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00628

AC XY:

4570

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00216

Gnomad4 FIN exome

AF:

0.00545

Gnomad4 NFE exome

AF:

0.00718

Gnomad4 OTH exome

AF:

0.00533

GnomAD4 genome

AF:

0.00440

AC:

670

AN:

152318

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00616

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00634

Hom.:

Bravo

AF:

0.00464

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00474

AC:

575

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00516

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	CYSLTR2: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.14

DANN

Benign

0.17

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.15

.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.57

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

2.0

.;N

REVEL

Benign

0.045

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.093

MVP

0.16

MPC

0.16

ClinPred

0.00020

GERP RS

1.3

Varity_R

0.075

gMVP

0.041

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over