Variant rs2236533 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.180-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,601,644 control chromosomes in the GnomAD database, including 57,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4658 hom., cov: 33)

Exomes 𝑓: 0.26 ( 52351 hom. )

Consequence

CXCL12
NM_199168.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.667

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=-0.82).

BP6

Variant 10-44378768-G-A is Benign according to our data. Variant chr10-44378768-G-A is described in ClinVar as [Benign]. Clinvar id is 1246518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_199168.4 link	c.180-45C>T		intron_variant		ENST00000343575.11	NP_954637.1	P48061-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11 link	c.180-45C>T		intron_variant		1	NM_199168.4	ENSP00000339913.6		P48061-2

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34120

AN:

152070

Hom.:

4657

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0852

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.277

AC:

69506

AN:

250952

Hom.:

11215

AF XY:

0.271

AC XY:

36785

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.0778

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.262

AC:

379416

AN:

1449456

Hom.:

52351

Cov.:

AF XY:

0.260

AC XY:

187669

AN XY:

721928

show subpopulations

Gnomad4 AFR exome

AF:

0.0748

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.224

AC:

34124

AN:

152188

Hom.:

4658

Cov.:

AF XY:

0.231

AC XY:

17193

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0850

Gnomad4 AMR

AF:

0.390

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.259

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.240

Hom.:

1032

Bravo

AF:

0.225

Asia WGS

AF:

0.177

AC:

614

AN:

3478

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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.9

DANN

Benign

0.77

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