10-44374567-C-T

Position:

• chr10-44374567-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.110-1477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 455,868 control chromosomes in the GnomAD database, including 4,578 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 (1346 hom., cov: 33)
  • Exomes 𝑓: 0.14 (3232 hom.)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.110-1477G>A		intron_variant			NP_001264919.1
CXCL12	NM_000609.7	c.267-1224G>A		intron_variant			NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-1224G>A		intron_variant		1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-1477G>A		intron_variant		5		ENSP00000379139.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19772 AN: 151988 Hom.: 1350 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.137 AC: 17608 AN: 128104 Hom.: 1261 AF XY: 0.141 AC XY: 9872 AN XY: 70154

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0981

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.143 AC: 43564 AN: 303762 Hom.: 3232 Cov.: 0 AF XY: 0.147 AC XY: 25488 AN XY: 172984

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.130 AC: 19779 AN: 152106 Hom.: 1346 Cov.: 33 AF XY: 0.129 AC XY: 9555 AN XY: 74340

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.142

Alfa AF: 0.137 Hom.: 1552

Bravo AF: 0.128

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.021
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266088; hg19: chr10-44870015; COSMIC: COSV59107466; COSMIC: COSV59107466;