rs266089

Variant names:

• chr10-44373979-A-G
• rs266089
• ENST00000374429.6:c.267-636T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.89).
• 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 rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.110-889T>C		intron_variant	Intron 2 of 2		NP_001264919.1
CXCL12	NM_000609.7	c.267-636T>C		intron_variant	Intron 3 of 3		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-636T>C		intron_variant	Intron 3 of 3	1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-889T>C		intron_variant	Intron 2 of 2	5		ENSP00000379139.3

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

African (AFR) AF: 0.705 AC: 29232 AN: 41454

American (AMR) AF: 0.910 AC: 13918 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2948 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4365 AN: 5152

South Asian (SAS) AF: 0.849 AC: 4092 AN: 4818

European-Finnish (FIN) AF: 0.934 AC: 9923 AN: 10624

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58479 AN: 67998

Other (OTH) AF: 0.860 AC: 1819 AN: 2114

Alfa AF: 0.849 Hom.: 57504

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
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs266089; hg19: chr10-44869427;