10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_199168.4(CXCL12):c.-11_-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 0.00285 in 409,864 control chromosomes in the GnomAD database, including 43 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (43 hom.)
• Consequence: CXCL12 NM_199168.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-44385008-CGCGGGCGG-C is Benign according to our data. Variant chr10-44385008-CGCGGGCGG-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 9 gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000937 AC: 112 AN: 119518 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000961

Gnomad ASJ AF: 0.0223

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000278

Gnomad OTH AF: 0.00246

GnomAD3 exomes AF: 0.00284 AC: 162 AN: 57116 Hom.: 9 AF XY: 0.00251 AC XY: 85 AN XY: 33858

Gnomad AFR exome AF: 0.00325

Gnomad AMR exome AF: 0.00305

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000543

Gnomad FIN exome AF: 0.000292

Gnomad NFE exome AF: 0.000803

Gnomad OTH exome AF: 0.00192

GnomAD4 exome AF: 0.00363 AC: 1055 AN: 290314 Hom.: 43 AF XY: 0.00323 AC XY: 514 AN XY: 158922

Gnomad4 AFR exome AF: 0.00365

Gnomad4 AMR exome AF: 0.00357

Gnomad4 ASJ exome AF: 0.0435

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000436

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.00249

Gnomad4 OTH exome AF: 0.00731

GnomAD4 genome AF: 0.000954 AC: 114 AN: 119550 Hom.: 0 Cov.: 0 AF XY: 0.000980 AC XY: 56 AN XY: 57164

Gnomad4 AFR AF: 0.000426

Gnomad4 AMR AF: 0.000959

Gnomad4 ASJ AF: 0.0223

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000278

Gnomad4 OTH AF: 0.00244

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

CXCL12: BP4, BS2 -

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;