rs17540465

Positions:

• chr10-44384928-C-T

Variant summary

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

The NM_199168.4(CXCL12):​c.61+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,541,632 control chromosomes in the GnomAD database, including 1,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (222 hom., cov: 31)
  • Exomes 𝑓: 0.035 (983 hom.)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.401

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=-0.76).
• BP6: Variant 10-44384928-C-T is Benign according to our data. Variant chr10-44384928-C-T is described in ClinVar as [Benign]. Clinvar id is 1273360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.61+17G>A		intron_variant		ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.61+17G>A		intron_variant		1	NM_199168.4	ENSP00000339913	P4

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7335 AN: 147132 Hom.: 222 Cov.: 31

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0151

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0399

GnomAD3 exomes AF: 0.0415 AC: 6520 AN: 157008 Hom.: 193 AF XY: 0.0420 AC XY: 3683 AN XY: 87780

Gnomad AFR exome AF: 0.0915

Gnomad AMR exome AF: 0.0459

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.0609

Gnomad SAS exome AF: 0.0551

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.0331

Gnomad OTH exome AF: 0.0372

GnomAD4 exome AF: 0.0346 AC: 48197 AN: 1394392 Hom.: 983 Cov.: 33 AF XY: 0.0354 AC XY: 24449 AN XY: 691126

Gnomad4 AFR exome AF: 0.0822

Gnomad4 AMR exome AF: 0.0452

Gnomad4 ASJ exome AF: 0.0161

Gnomad4 EAS exome AF: 0.0428

Gnomad4 SAS exome AF: 0.0577

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.0315

Gnomad4 OTH exome AF: 0.0388

GnomAD4 genome AF: 0.0499 AC: 7347 AN: 147240 Hom.: 222 Cov.: 31 AF XY: 0.0489 AC XY: 3523 AN XY: 72112

Gnomad4 AFR AF: 0.0944

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.0151

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.0606

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0390

Alfa AF: 0.0393 Hom.: 32

Bravo AF: 0.0508

Asia WGS AF: 0.0590 AC: 205 AN: 3468

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	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17540465; hg19: chr10-44880376;