10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGGGCGGGCGG

Variant names:

• chr10-44385008-C-CGCGGGCGGGCGG
• rs76444314
• NM_199168.4:c.-15_-4dupCCGCCCGCCCGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_199168.4(CXCL12):​c.-15_-4dupCCGCCCGCCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 293,020 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CXCL12 NM_199168.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• Publications: 0 publications found

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]

ENSG00000303087 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.-15_-4dupCCGCCCGCCCGC		5_prime_UTR_variant	Exon 1 of 3	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.-15_-4dupCCGCCCGCCCGC		5_prime_UTR_variant	Exon 1 of 3	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes AF: 0.0000586 AC: 7 AN: 119524 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000174

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 6 AN: 293020 Hom.: 0 Cov.: 32 AF XY: 0.00000624 AC XY: 1 AN XY: 160284

African (AFR) AF: 0.00 AC: 0 AN: 7746

American (AMR) AF: 0.00 AC: 0 AN: 13858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8876

East Asian (EAS) AF: 0.000312 AC: 1 AN: 3210

South Asian (SAS) AF: 0.00 AC: 0 AN: 41470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1102

European-Non Finnish (NFE) AF: 0.00000515 AC: 1 AN: 194002

Other (OTH) AF: 0.000312 AC: 4 AN: 12802

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000586 AC: 7 AN: 119524 Hom.: 0 Cov.: 28 AF XY: 0.0000700 AC XY: 4 AN XY: 57140

African (AFR) AF: 0.00 AC: 0 AN: 32840

American (AMR) AF: 0.00 AC: 0 AN: 11446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3100

East Asian (EAS) AF: 0.00176 AC: 6 AN: 3416

South Asian (SAS) AF: 0.00 AC: 0 AN: 3066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000174 AC: 1 AN: 57562

Other (OTH) AF: 0.00 AC: 0 AN: 1626

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69

Splicing

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

Other links and lift over

dbSNP: rs76444314; hg19: chr10-44880456;