10-44378861-G-T

Variant summary

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

The NM_199168.4(CXCL12):c.180-138C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 797,266 control chromosomes in the GnomAD database, including 16,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2738 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13722 hom.)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.985

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=-0.8).
• BP6: Variant 10-44378861-G-T is Benign according to our data. Variant chr10-44378861-G-T is described in ClinVar as [Benign]. Clinvar id is 1234302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_199168.4	c.180-138C>A		intron_variant		ENST00000343575.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000343575.11	c.180-138C>A		intron_variant		1	NM_199168.4	P4

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25250 AN: 152124 Hom.: 2737 Cov.: 33

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.198 AC: 128000 AN: 645024 Hom.: 13722 AF XY: 0.194 AC XY: 65890 AN XY: 340106

Gnomad4 AFR exome AF: 0.0381

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.166 AC: 25250 AN: 152242 Hom.: 2738 Cov.: 33 AF XY: 0.169 AC XY: 12608 AN XY: 74434

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.203

Alfa AF: 0.140 Hom.: 499

Bravo AF: 0.171

Asia WGS AF: 0.117 AC: 408 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 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2236534; hg19: chr10-44874309;