Variant rs17540465 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.401

Variant links:

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]

CXCL12 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CXCL12	NM_199168.4 link	c.61+17G>A		intron_variant	Intron 1 of 2	ENST00000343575.11	NP_954637.1	P48061-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11 link	c.61+17G>A		intron_variant	Intron 1 of 2	1	NM_199168.4	ENSP00000339913.6		P48061-2

Frequencies

GnomAD3 genomes

AF:

0.0499

AC:

7335

AN:

147132

Hom.:

222

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0354

AC XY:

24449

AN XY:

691126

show subpopulations

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.:

AF XY:

0.0489

AC XY:

3523

AN XY:

72112

show subpopulations

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.:

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over