10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_199168.4(CXCL12):c.-4_-3insCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 412,500 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0058 (1 hom., cov: 28)
  • Exomes 𝑓: 0.0036 (2 hom.)
• Consequence: CXCL12 NM_199168.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_199168.4	c.-4_-3insCCGC		5_prime_UTR_variant	1/3	ENST00000343575.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000343575.11	c.-4_-3insCCGC		5_prime_UTR_variant	1/3	1	NM_199168.4	P4

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 697 AN: 119510 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00904

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00294

Gnomad FIN AF: 0.000184

Gnomad MID AF: 0.00368

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00677

GnomAD3 exomes AF: 0.00137 AC: 78 AN: 57116 Hom.: 0 AF XY: 0.00142 AC XY: 48 AN XY: 33858

Gnomad AFR exome AF: 0.00325

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.00611

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000699

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00128

GnomAD4 exome AF: 0.00357 AC: 1045 AN: 292958 Hom.: 2 Cov.: 32 AF XY: 0.00369 AC XY: 591 AN XY: 160248

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.000935

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.00151

Gnomad4 NFE exome AF: 0.00343

Gnomad4 OTH exome AF: 0.00610

GnomAD4 genome AF: 0.00581 AC: 695 AN: 119542 Hom.: 1 Cov.: 28 AF XY: 0.00537 AC XY: 307 AN XY: 57158

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00904

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00294

Gnomad4 FIN AF: 0.000184

Gnomad4 NFE AF: 0.00313

Gnomad4 OTH AF: 0.00671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76444314; hg19: chr10-44880456;