rs266089

Positions:

• chr10-44373979-A-G
• chr10-44373979-A-T

Variant summary

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

The ENST00000374429.6(CXCL12):​c.267-636T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,136 control chromosomes in the GnomAD database, including 52,430 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 0.83 (52430 hom., cov: 33)
• Consequence: CXCL12 ENST00000374429.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_000609.7	c.267-636T>C		intron_variant
CXCL12	NM_001277990.2	c.110-889T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-636T>C		intron_variant		1		A1
CXCL12	ENST00000395793.7	c.110-889T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125700 AN: 152018 Hom.: 52387 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.859

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

GnomAD4 genome AF: 0.827 AC: 125796 AN: 152136 Hom.: 52430 Cov.: 33 AF XY: 0.832 AC XY: 61884 AN XY: 74364

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.910

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.860

Alfa AF: 0.853 Hom.: 45258

Bravo AF: 0.820

Asia WGS AF: 0.831 AC: 2886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266089; hg19: chr10-44869427;