chr2-136116434-A-G

Position:

• chr2-136116434-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003467.3(CXCR4):​c.16-522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,910 control chromosomes in the GnomAD database, including 8,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.30 (8723 hom., cov: 31)
• Consequence: CXCR4 NM_003467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.570

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-136116434-A-G is Benign according to our data. Variant chr2-136116434-A-G is described in ClinVar as [Benign]. Clinvar id is 1279307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR4	NM_003467.3	c.16-522T>C		intron_variant		ENST00000241393.4	NP_003458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR4	ENST00000241393.4	c.16-522T>C		intron_variant		1	NM_003467.3	ENSP00000241393	P2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45872 AN: 151794 Hom.: 8701 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.302 AC: 45952 AN: 151910 Hom.: 8723 Cov.: 31 AF XY: 0.295 AC XY: 21911 AN XY: 74254

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0378

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.265

Alfa AF: 0.265 Hom.: 1014

Bravo AF: 0.323

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2471859; hg19: chr2-136874004;