10-44370760-C-G

Variant summary

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

The ENST00000374429.6(CXCL12):c.*2568G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,156 control chromosomes in the GnomAD database, including 28,009 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 0.60 (28005 hom., cov: 33)
  • Exomes 𝑓: 0.46 (4 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_000609.7	c.*2568G>C		3_prime_UTR_variant	4/4
CXCL12	NM_001277990.2	c.*2128G>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000374429.6	c.*2568G>C		3_prime_UTR_variant	4/4	1		A1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90742 AN: 151992 Hom.: 27980 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.648

GnomAD4 exome AF: 0.457 AC: 21 AN: 46 Hom.: 4 Cov.: 0 AF XY: 0.533 AC XY: 16 AN XY: 30

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.597 AC: 90809 AN: 152110 Hom.: 28005 Cov.: 33 AF XY: 0.607 AC XY: 45145 AN XY: 74364

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.653

Alfa AF: 0.472 Hom.: 1307

Bravo AF: 0.593

Asia WGS AF: 0.733 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.7
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266093; hg19: chr10-44866208;