10-44373408-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000374429.6(CXCL12):c.267-65T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,449,630 control chromosomes in the GnomAD database, including 530,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.84 (53777 hom., cov: 34)
  • Exomes 𝑓: 0.86 (477183 hom.)
• Consequence: CXCL12 ENST00000374429.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-44373408-A-C is Benign according to our data. Variant chr10-44373408-A-C is described in ClinVar as [Benign]. Clinvar id is 1280296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_000609.7	c.267-65T>G		intron_variant
CXCL12	NM_001277990.2	c.110-318T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-65T>G		intron_variant		1		A1
CXCL12	ENST00000395793.7	c.110-318T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127537 AN: 152120 Hom.: 53730 Cov.: 34

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.868

GnomAD4 exome AF: 0.857 AC: 1111998 AN: 1297392 Hom.: 477183 AF XY: 0.857 AC XY: 557043 AN XY: 649856

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.842

Gnomad4 SAS exome AF: 0.853

Gnomad4 FIN exome AF: 0.922

Gnomad4 NFE exome AF: 0.855

Gnomad4 OTH exome AF: 0.858

GnomAD4 genome AF: 0.838 AC: 127638 AN: 152238 Hom.: 53777 Cov.: 34 AF XY: 0.843 AC XY: 62768 AN XY: 74422

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.869

Alfa AF: 0.846 Hom.: 7194

Bravo AF: 0.834

Asia WGS AF: 0.836 AC: 2905 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.5
Dann	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266091; hg19: chr10-44868856; COSMIC: COSV59107387; COSMIC: COSV59107387;