rs197452

Positions:

• chr10-44374792-C-T

Variant summary

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

The NM_001277990.2(CXCL12):​c.110-1702G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 413,592 control chromosomes in the GnomAD database, including 4,207 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 0.13 (1426 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2781 hom.)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.89

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.110-1702G>A		intron_variant			NP_001264919.1
CXCL12	NM_000609.7	c.267-1449G>A		intron_variant			NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-1449G>A		intron_variant		1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-1702G>A		intron_variant		5		ENSP00000379139.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20304 AN: 151832 Hom.: 1430 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.144 AC: 37605 AN: 261642 Hom.: 2781 AF XY: 0.147 AC XY: 21534 AN XY: 146028

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.0990

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.134 AC: 20310 AN: 151950 Hom.: 1426 Cov.: 32 AF XY: 0.132 AC XY: 9812 AN XY: 74244

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0960

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.150

Alfa AF: 0.144 Hom.: 803

Bravo AF: 0.132

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0030
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs197452; hg19: chr10-44870240;