rs2839689

Positions:

• chr10-44380011-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199168.4(CXCL12):​c.179+752A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,130 control chromosomes in the GnomAD database, including 2,747 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 0.19 (2747 hom., cov: 33)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

Genes affected

CXCL12 (HGNC:10672): (C-X-C motif chemokine ligand 12) This antimicrobial gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_199168.4	c.179+752A>T		intron_variant		ENST00000343575.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000343575.11	c.179+752A>T		intron_variant		1	NM_199168.4	P4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28228 AN: 152012 Hom.: 2746 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0572

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.186 AC: 28234 AN: 152130 Hom.: 2747 Cov.: 33 AF XY: 0.182 AC XY: 13516 AN XY: 74374

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0567

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.174

Alfa AF: 0.205 Hom.: 468

Bravo AF: 0.181

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.5
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs2839689; hg19: chr10-44875459;