Genetic Variant CXCL12:c.267-1224G>A (chr10-44374567-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000374429.6(CXCL12):c.267-1224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 455,868 control chromosomes in the GnomAD database, including 4,578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1346 hom., cov: 33)

Exomes 𝑓: 0.14 ( 3232 hom. )

Consequence

CXCL12
ENST00000374429.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.42

Publications

8 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2 link	c.110-1477G>A		intron_variant	Intron 2 of 2		NP_001264919.1	P48061-7
CXCL12	NM_000609.7 link	c.267-1224G>A		intron_variant	Intron 3 of 3		NP_000600.1	P48061-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6 link	c.267-1224G>A		intron_variant	Intron 3 of 3	1		ENSP00000363551.2		P48061-1
CXCL12	ENST00000395793.7 link	c.110-1477G>A		intron_variant	Intron 2 of 2	5		ENSP00000379139.3		P48061-7

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19772

AN:

151988

Hom.:

1350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.143

GnomAD2 exomes

AF:

0.137

AC:

17608

AN:

128104

AF XY:

0.141

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0981

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.143

AC:

43564

AN:

303762

Hom.:

3232

Cov.:

AF XY:

0.147

AC XY:

25488

AN XY:

172984

show subpopulations

African (AFR)

AF:

0.113

AC:

974

AN:

8620

American (AMR)

AF:

0.110

AC:

2998

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

1621

AN:

10786

East Asian (EAS)

AF:

0.105

AC:

968

AN:

9210

South Asian (SAS)

AF:

0.173

AC:

10357

AN:

59736

European-Finnish (FIN)

AF:

0.114

AC:

1416

AN:

12368

Middle Eastern (MID)

AF:

0.151

AC:

418

AN:

2776

European-Non Finnish (NFE)

AF:

0.144

AC:

22837

AN:

158776

Other (OTH)

AF:

0.139

AC:

1975

AN:

14216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3506

7012

10517

14023

17529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19779

AN:

152106

Hom.:

1346

Cov.:

AF XY:

0.129

AC XY:

9555

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.111

AC:

4601

AN:

41490

American (AMR)

AF:

0.123

AC:

1887

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

513

AN:

3472

East Asian (EAS)

AF:

0.104

AC:

537

AN:

5160

South Asian (SAS)

AF:

0.165

AC:

795

AN:

4816

European-Finnish (FIN)

AF:

0.116

AC:

1226

AN:

10584

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9803

AN:

67988

Other (OTH)

AF:

0.142

AC:

299

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

884

1768

2653

3537

4421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.136

Hom.:

1943

Bravo

AF:

0.128

Asia WGS

AF:

0.101

AC:

351

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.021

(source)

DANN

Benign

0.51

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over