rs266087

Variant names:

• chr10-44375614-G-A
• rs266087
• ENST00000374429.6:c.267-2271C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-44375614-G-A
• chr10-44375614-G-C
• chr10-44375614-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374429.6(CXCL12):​c.267-2271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,168 control chromosomes in the GnomAD database, including 8,503 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 0.32 (8503 hom., cov: 34)
• Consequence: CXCL12 ENST00000374429.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.110-2524C>T		intron_variant	Intron 2 of 2		NP_001264919.1
CXCL12	NM_000609.7	c.267-2271C>T		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.267-2271C>T		intron_variant	Intron 3 of 3	1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-2524C>T		intron_variant	Intron 2 of 2	5		ENSP00000379139.3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49354 AN: 152048 Hom.: 8496 Cov.: 34

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.325 AC: 49384 AN: 152168 Hom.: 8503 Cov.: 34 AF XY: 0.325 AC XY: 24190 AN XY: 74376

African (AFR) AF: 0.231 AC: 9585 AN: 41524

American (AMR) AF: 0.321 AC: 4912 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2727 AN: 5160

South Asian (SAS) AF: 0.437 AC: 2105 AN: 4818

European-Finnish (FIN) AF: 0.318 AC: 3368 AN: 10596

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24073 AN: 67984

Other (OTH) AF: 0.373 AC: 788 AN: 2112

Alfa AF: 0.344 Hom.: 25994

Bravo AF: 0.317

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.030
DANN	Benign	0.69
PhyloP100		-1.8
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: rs266087; hg19: chr10-44871062;