10-44378631-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000395794.2(CXCL12):c.266+6C>T variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.0000171 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
CXCL12
ENST00000395794.2 splice_donor_region, intron
ENST00000395794.2 splice_donor_region, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.85
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CXCL12 | NM_199168.4 | c.*2C>T | 3_prime_UTR_variant | 3/3 | ENST00000343575.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CXCL12 | ENST00000343575.11 | c.*2C>T | 3_prime_UTR_variant | 3/3 | 1 | NM_199168.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251480Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135916
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461848Hom.: 0 Cov.: 34 AF XY: 0.0000261 AC XY: 19AN XY: 727226
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Susceptibility to HIV infection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | CXCL12 NM_000609 exon 3 c.266+6C>T: This variant has not been reported in the literature but is present in 6/30782 South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs749856360). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at