10-44371698-A-G

Variant summary

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

The ENST00000374429.6(CXCL12):c.*1630T>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 0.272 in 153,258 control chromosomes in the GnomAD database, including 6,292 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 0.27 (6251 hom., cov: 33)
  • Exomes 𝑓: 0.27 (41 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_000609.7	c.*1630T>C		3_prime_UTR_variant	4/4
CXCL12	NM_001277990.2	c.*1190T>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000374429.6	c.*1630T>C		3_prime_UTR_variant	4/4	1		A1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41313 AN: 152076 Hom.: 6248 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.267 AC: 284 AN: 1064 Hom.: 41 Cov.: 0 AF XY: 0.254 AC XY: 159 AN XY: 626

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.272 AC: 41333 AN: 152194 Hom.: 6251 Cov.: 33 AF XY: 0.277 AC XY: 20620 AN XY: 74380

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.285

Alfa AF: 0.297 Hom.: 8001

Bravo AF: 0.275

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.29
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1029153; hg19: chr10-44867146;