rs2839696

Positions:

• chr10-44371180-G-A
• chr10-44371180-G-T

Variant summary

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

The ENST00000374429.6(CXCL12):​c.*2148C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 248,208 control chromosomes in the GnomAD database, including 267 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 0.046 (185 hom., cov: 33)
  • Exomes 𝑓: 0.041 (82 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_000609.7	c.*2148C>T		3_prime_UTR_variant	4/4		NP_000600.1
CXCL12	NM_001277990.2	c.*1708C>T		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.*2148C>T		3_prime_UTR_variant	4/4	1		ENSP00000363551	A1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6921 AN: 152224 Hom.: 185 Cov.: 33

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0406 AC: 3890 AN: 95866 Hom.: 82 Cov.: 0 AF XY: 0.0424 AC XY: 2346 AN XY: 55358

Gnomad4 AFR exome AF: 0.0813

Gnomad4 AMR exome AF: 0.0454

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.0574

Gnomad4 SAS exome AF: 0.0601

Gnomad4 FIN exome AF: 0.0210

Gnomad4 NFE exome AF: 0.0340

Gnomad4 OTH exome AF: 0.0400

GnomAD4 genome AF: 0.0455 AC: 6935 AN: 152342 Hom.: 185 Cov.: 33 AF XY: 0.0446 AC XY: 3320 AN XY: 74506

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0333

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0343 Hom.: 103

Bravo AF: 0.0475

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2839696; hg19: chr10-44866628;