rs2297630

Positions:

• chr10-44376100-G-A
• chr10-44376100-G-C
• chr10-44376100-G-T

Variant summary

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

The ENST00000374426.6(CXCL12):​c.267-68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,561,326 control chromosomes in the GnomAD database, including 55,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4529 hom., cov: 34)
  • Exomes 𝑓: 0.26 (50606 hom.)
• Consequence: CXCL12 ENST00000374426.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.11

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 10-44376100-G-A is Benign according to our data. Variant chr10-44376100-G-A is described in ClinVar as [Benign]. Clinvar id is 1250974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_000609.7	c.266+2537C>T		intron_variant			NP_000600.1
CXCL12	NM_001033886.2	c.267-68C>T		intron_variant			NP_001029058.1
CXCL12	NM_001277990.2	c.110-3010C>T		intron_variant			NP_001264919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374426.6	c.267-68C>T		intron_variant		1		ENSP00000363548
CXCL12	ENST00000374429.6	c.266+2537C>T		intron_variant		1		ENSP00000363551	A1
CXCL12	ENST00000395793.7	c.110-3010C>T		intron_variant		5		ENSP00000379139

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32942 AN: 152050 Hom.: 4528 Cov.: 34

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.262 AC: 368668 AN: 1409158 Hom.: 50606 AF XY: 0.260 AC XY: 182597 AN XY: 703050

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.216 AC: 32941 AN: 152168 Hom.: 4529 Cov.: 34 AF XY: 0.223 AC XY: 16622 AN XY: 74380

Gnomad4 AFR AF: 0.0599

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.244

Alfa AF: 0.249 Hom.: 6747

Bravo AF: 0.216

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.58
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2297630; hg19: chr10-44871548;