rs266087

Positions:

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

Variant summary

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

The NM_001277990.2(CXCL12):​c.110-2524C>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 NM_001277990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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=-0.9).
• 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/exons	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.110-2524C>T		intron_variant			NP_001264919.1
CXCL12	NM_000609.7	c.267-2271C>T		intron_variant			NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-2271C>T		intron_variant		1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-2524C>T		intron_variant		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

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.373

Alfa AF: 0.356 Hom.: 12149

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266087; hg19: chr10-44871062;