10-44373017-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000374429.6(CXCL12):c.*311G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,536,038 control chromosomes in the GnomAD database, including 1,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (185 hom., cov: 33)
  • Exomes 𝑓: 0.035 (956 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-44373017-C-T is Benign according to our data. Variant chr10-44373017-C-T is described in ClinVar as [Benign]. Clinvar id is 1233193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_001277990.2	c.183G>A	p.Leu61=	synonymous_variant	3/3
CXCL12	NM_000609.7	c.*311G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000374429.6	c.*311G>A		3_prime_UTR_variant	4/4	1		A1
CXCL12	ENST00000395793.7	c.183G>A	p.Leu61=	synonymous_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6922 AN: 152194 Hom.: 185 Cov.: 33

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0422 AC: 5774 AN: 136852 Hom.: 164 AF XY: 0.0425 AC XY: 3163 AN XY: 74366

Gnomad AFR exome AF: 0.0692

Gnomad AMR exome AF: 0.0462

Gnomad ASJ exome AF: 0.0180

Gnomad EAS exome AF: 0.0633

Gnomad SAS exome AF: 0.0557

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0335

Gnomad OTH exome AF: 0.0409

GnomAD4 exome AF: 0.0345 AC: 47760 AN: 1383726 Hom.: 956 Cov.: 34 AF XY: 0.0353 AC XY: 24104 AN XY: 682802

Gnomad4 AFR exome AF: 0.0706

Gnomad4 AMR exome AF: 0.0453

Gnomad4 ASJ exome AF: 0.0158

Gnomad4 EAS exome AF: 0.0442

Gnomad4 SAS exome AF: 0.0579

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.0316

Gnomad4 OTH exome AF: 0.0381

GnomAD4 genome AF: 0.0456 AC: 6939 AN: 152312 Hom.: 185 Cov.: 33 AF XY: 0.0445 AC XY: 3315 AN XY: 74484

Gnomad4 AFR AF: 0.0749

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0333

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0329 Hom.: 104

Bravo AF: 0.0476

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CXCL12-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.30
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12258838; hg19: chr10-44868465;