rs2228014

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003467.3(CXCR4):c.414C>T(p.Ile138=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,614,162 control chromosomes in the GnomAD database, including 1,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 171 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1484 hom. )

Consequence

CXCR4
NM_003467.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.486

Variant links:

Genes affected

CXCR4 (HGNC:2561): (C-X-C motif chemokine receptor 4) This gene encodes a CXC chemokine receptor specific for stromal cell-derived factor-1. The protein has 7 transmembrane regions and is located on the cell surface. It acts with the CD4 protein to support HIV entry into cells and is also highly expressed in breast cancer cells. Mutations in this gene have been associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

CXCR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-136115514-G-A is Benign according to our data. Variant chr2-136115514-G-A is described in ClinVar as [Benign]. Clinvar id is 259052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-136115514-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.486 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCR4	NM_003467.3 linkuse as main transcript	c.414C>T	p.Ile138=	synonymous_variant	2/2	ENST00000241393.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR4	ENST00000241393.4 linkuse as main transcript	c.414C>T	p.Ile138=	synonymous_variant	2/2	1	NM_003467.3	P2	P61073-1

Frequencies

GnomAD3 genomes

AF:

0.0368

AC:

5594

AN:

152154

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.0771

Gnomad AMR

AF:

0.0329

Gnomad ASJ

AF:

0.0746

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0814

Gnomad FIN

AF:

0.00960

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0484

GnomAD3 exomes

AF:

0.0457

AC:

11496

AN:

251468

Hom.:

438

AF XY:

0.0483

AC XY:

6561

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.0201

Gnomad ASJ exome

AF:

0.0720

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.0807

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0394

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0394

AC:

57578

AN:

1461890

Hom.:

1484

Cov.:

AF XY:

0.0412

AC XY:

29935

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0732

Gnomad4 EAS exome

AF:

0.0977

Gnomad4 SAS exome

AF:

0.0791

Gnomad4 FIN exome

AF:

0.0128

Gnomad4 NFE exome

AF:

0.0356

Gnomad4 OTH exome

AF:

0.0460

GnomAD4 genome

AF:

0.0368

AC:

5597

AN:

152272

Hom.:

171

Cov.:

AF XY:

0.0377

AC XY:

2804

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.0329

Gnomad4 ASJ

AF:

0.0746

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.0813

Gnomad4 FIN

AF:

0.00960

Gnomad4 NFE

AF:

0.0407

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0424

Hom.:

232

Bravo

AF:

0.0363

Asia WGS

AF:

0.0990

AC:

343

AN:

3478

EpiCase

AF:

0.0451

EpiControl

AF:

0.0468

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Warts, hypogammaglobulinemia, infections, and myelokathexis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 06, 2020

This variant is associated with the following publications: (PMID: 19473177, 31177127) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

Cadd

Benign

2.3

Dann

Benign

0.83

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