dbSNP rs197452: CXCL12:c.267-1449G>A (chr10-44374792-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.267-1449G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 413,592 control chromosomes in the GnomAD database, including 4,207 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 ( 1426 hom., cov: 32)

Exomes 𝑓: 0.14 ( 2781 hom. )

Consequence

CXCL12
ENST00000374429.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.89

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:

Genome browser will be placed here

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=-1.02).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2 link	c.110-1702G>A		intron_variant	Intron 2 of 2		NP_001264919.1	P48061-7
CXCL12	NM_000609.7 link	c.267-1449G>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.267-1449G>A		intron_variant	Intron 3 of 3	1		ENSP00000363551.2		P48061-1
CXCL12	ENST00000395793.7 link	c.110-1702G>A		intron_variant	Intron 2 of 2	5		ENSP00000379139.3		P48061-7

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20304

AN:

151832

Hom.:

1430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0958

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.144

AC:

37605

AN:

261642

Hom.:

2781

AF XY:

0.147

AC XY:

21534

AN XY:

146028

show subpopulations

African (AFR)

AF:

0.110

AC:

839

AN:

7618

American (AMR)

AF:

0.112

AC:

2710

AN:

24304

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

1187

AN:

7844

East Asian (EAS)

AF:

0.0990

AC:

875

AN:

8834

South Asian (SAS)

AF:

0.172

AC:

8801

AN:

51170

European-Finnish (FIN)

AF:

0.115

AC:

1229

AN:

10692

Middle Eastern (MID)

AF:

0.151

AC:

383

AN:

2540

European-Non Finnish (NFE)

AF:

0.146

AC:

19840

AN:

136214

Other (OTH)

AF:

0.140

AC:

1741

AN:

12426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1779

3558

5338

7117

8896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<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:

0.134

AC:

20310

AN:

151950

Hom.:

1426

Cov.:

AF XY:

0.132

AC XY:

9812

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.112

AC:

4648

AN:

41464

American (AMR)

AF:

0.132

AC:

2019

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

535

AN:

3464

East Asian (EAS)

AF:

0.0960

AC:

494

AN:

5146

South Asian (SAS)

AF:

0.166

AC:

797

AN:

4794

European-Finnish (FIN)

AF:

0.116

AC:

1227

AN:

10536

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10156

AN:

67958

Other (OTH)

AF:

0.150

AC:

316

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

907

1814

2721

3628

4535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.145

Hom.:

901

Bravo

AF:

0.132

Asia WGS

AF:

0.0990

AC:

343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0030

(source)

DANN

Benign

0.75

PhyloP100

-4.9

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