10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGGGCGG

Variant summary

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

The NM_199168.4(CXCL12):c.-4_-3insCCGCCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 293,022 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 0.000092 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• 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 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.-4_-3insCCGCCCGC		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_-3insCCGCCCGC		5_prime_UTR_variant	1/3	1	NM_199168.4	P4

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 11 AN: 119524 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000368

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000139

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000444 AC: 13 AN: 293022 Hom.: 0 Cov.: 32 AF XY: 0.0000374 AC XY: 6 AN XY: 160284

Gnomad4 AFR exome AF: 0.000129

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000312

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000100

Gnomad4 NFE exome AF: 0.0000464

Gnomad4 OTH exome AF: 0.0000781

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000920 AC: 11 AN: 119524 Hom.: 0 Cov.: 28 AF XY: 0.0000350 AC XY: 2 AN XY: 57140

Gnomad4 AFR AF: 0.0000305

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000368

Gnomad4 NFE AF: 0.000139

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;