14-24316578-C-T

Variant names:

• chr14-24316578-C-T
• rs1046584
• NM_001143919.3:c.927C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001143919.3(LTB4R):​c.927C>T​(p.Gly309Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,442,756 control chromosomes in the GnomAD database, including 18,843 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 0.13 (1911 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16932 hom.)
• Consequence: LTB4R NM_001143919.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=-0.383 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTB4R	NM_001143919.3	c.927C>T	p.Gly309Gly	synonymous_variant	Exon 2 of 2	ENST00000345363.8	NP_001137391.1
LTB4R	NM_181657.3	c.927C>T	p.Gly309Gly	synonymous_variant	Exon 2 of 2		NP_858043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTB4R	ENST00000345363.8	c.927C>T	p.Gly309Gly	synonymous_variant	Exon 2 of 2	1	NM_001143919.3	ENSP00000307445.3
LTB4R	ENST00000396782.2	c.927C>T	p.Gly309Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000380002.2
LTB4R	ENST00000396789.4	c.927C>T	p.Gly309Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000380008.4
LTB4R	ENST00000556141.1	c.627C>T	p.Gly209Gly	synonymous_variant	Exon 2 of 2	3		ENSP00000451929.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20325 AN: 151934 Hom.: 1916 Cov.: 33

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.226 AC: 10719 AN: 47400 AF XY: 0.225

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.597

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.137 AC: 177265 AN: 1290714 Hom.: 16932 Cov.: 32 AF XY: 0.141 AC XY: 89116 AN XY: 633110

African (AFR) AF: 0.0889 AC: 2212 AN: 24892

American (AMR) AF: 0.172 AC: 2907 AN: 16940

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 2938 AN: 19750

East Asian (EAS) AF: 0.608 AC: 18184 AN: 29908

South Asian (SAS) AF: 0.271 AC: 17779 AN: 65552

European-Finnish (FIN) AF: 0.191 AC: 7391 AN: 38624

Middle Eastern (MID) AF: 0.121 AC: 488 AN: 4030

European-Non Finnish (NFE) AF: 0.113 AC: 117644 AN: 1037866

Other (OTH) AF: 0.145 AC: 7722 AN: 53152

GnomAD4 genome AF: 0.134 AC: 20306 AN: 152042 Hom.: 1911 Cov.: 33 AF XY: 0.143 AC XY: 10616 AN XY: 74322

African (AFR) AF: 0.0961 AC: 3990 AN: 41520

American (AMR) AF: 0.131 AC: 2005 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3468

East Asian (EAS) AF: 0.517 AC: 2661 AN: 5150

South Asian (SAS) AF: 0.282 AC: 1364 AN: 4830

European-Finnish (FIN) AF: 0.191 AC: 2010 AN: 10544

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.110 AC: 7463 AN: 67940

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.0780 Hom.: 145

Bravo AF: 0.128

Asia WGS AF: 0.378 AC: 1310 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.5
DANN	Benign	0.94
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs1046584; hg19: chr14-24785784; COSMIC: COSV60252897; COSMIC: COSV60252897;