rs76444314

chr10-44385008-CGCGGGCGGGCGGGCGG-Cchr10-44385008-CGCGGGCGGGCGGGCGG-CGCGGchr10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGchr10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGchr10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGGchr10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGGGCGGchr10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGGGCGGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_199168.4(CXCL12):c.-19_-4del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 412,336 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CXCL12 NM_199168.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_199168.4	c.-19_-4del		5_prime_UTR_variant	1/3	ENST00000343575.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000343575.11	c.-19_-4del		5_prime_UTR_variant	1/3	1	NM_199168.4	P4

Frequencies

GnomAD3 genomes AF: 0.0000335 AC: 4 AN: 119522 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000652

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000875 AC: 5 AN: 57116 Hom.: 1 AF XY: 0.000118 AC XY: 4 AN XY: 33858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000388

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000106 AC: 31 AN: 292782 Hom.: 0 AF XY: 0.0000937 AC XY: 15 AN XY: 160158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000144

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000169

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000980

Gnomad4 OTH exome AF: 0.000235

GnomAD4 genome AF: 0.0000335 AC: 4 AN: 119554 Hom.: 0 Cov.: 0 AF XY: 0.0000350 AC XY: 2 AN XY: 57164

Gnomad4 AFR AF: 0.0000608

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000652

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;