dbSNP rs1046584: LTB4R:p.Gly309Gly (chr14-24316578-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001143919.3(LTB4R):c.927C>A(p.Gly309Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

LTB4R
NM_001143919.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.383

Publications

14 publications found

Variant links:

Genes affected

LTB4R (HGNC:6713): (leukotriene B4 receptor) Predicted to enable G protein-coupled peptide receptor activity and leukotriene B4 receptor activity. Predicted to be involved in inflammatory response and neuropeptide signaling pathway. Predicted to act upstream of or within signal transduction. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LTB4R links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-0.383 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143919.3. 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
	LTB4R	NM_001143919.3	MANE Select	c.927C>A	p.Gly309Gly	synonymous	Exon 2 of 2	NP_001137391.1	Q15722
	LTB4R	NM_181657.3		c.927C>A	p.Gly309Gly	synonymous	Exon 2 of 2	NP_858043.1	Q15722

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTB4R	ENST00000345363.8	TSL:1 MANE Select	c.927C>A	p.Gly309Gly	synonymous	Exon 2 of 2	ENSP00000307445.3	Q15722
LTB4R	ENST00000396782.2	TSL:1	c.927C>A	p.Gly309Gly	synonymous	Exon 2 of 2	ENSP00000380002.2	Q15722
LTB4R	ENST00000396789.4	TSL:1	c.927C>A	p.Gly309Gly	synonymous	Exon 2 of 2	ENSP00000380008.4	Q15722

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD4 exome

AF:

7.75e-7

AC:

AN:

1290816

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

633182

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24894

American (AMR)

AF:

0.00

AC:

AN:

16952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19750

East Asian (EAS)

AF:

0.00

AC:

AN:

29910

South Asian (SAS)

AF:

0.00

AC:

AN:

65568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4032

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1037910

Other (OTH)

AF:

0.0000188

AC:

AN:

53158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151962

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67952

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

145

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.7

(source)

DANN

Benign

0.90

PhyloP100

-0.38

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over