rs1065297

Positions:

• chr10-44370528-A-G

Variant summary

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

The ENST00000374429.6(CXCL12):​c.*2800T>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 0.0535 in 152,268 control chromosomes in the GnomAD database, including 286 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 0.053 (286 hom., cov: 33)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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 (AFR) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_000609.7	c.*2800T>C		3_prime_UTR_variant	4/4		NP_000600.1
CXCL12	NM_001277990.2	c.*2360T>C		3_prime_UTR_variant	3/3		NP_001264919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.*2800T>C		3_prime_UTR_variant	4/4	1		ENSP00000363551	A1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8117 AN: 152128 Hom.: 284 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0441

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0535 AC: 8139 AN: 152246 Hom.: 286 Cov.: 33 AF XY: 0.0521 AC XY: 3878 AN XY: 74436

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0342

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0389 Hom.: 194

Bravo AF: 0.0566

Asia WGS AF: 0.0650 AC: 226 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	7.1
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1065297; hg19: chr10-44865976;