rs2839689

Variant names:

• chr10-44380011-T-A
• rs2839689
• NM_199168.4:c.179+752A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.179+752A>T		intron_variant	Intron 2 of 2	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.179+752A>T		intron_variant	Intron 2 of 2	1	NM_199168.4	ENSP00000339913.6

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

African (AFR) AF: 0.192 AC: 7984 AN: 41494

American (AMR) AF: 0.143 AC: 2189 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5172

South Asian (SAS) AF: 0.0567 AC: 273 AN: 4818

European-Finnish (FIN) AF: 0.215 AC: 2275 AN: 10586

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14302 AN: 67976

Other (OTH) AF: 0.174 AC: 368 AN: 2112

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
PhyloP100		2.6
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: rs2839689; hg19: chr10-44875459;