dbSNP rs12258838: CXCL12:c.*311G>A (chr10-44373017-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001277990.2(CXCL12):c.183G>A(p.Leu61Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,536,038 control chromosomes in the GnomAD database, including 1,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 185 hom., cov: 33)

Exomes 𝑓: 0.035 ( 956 hom. )

Consequence

CXCL12
NM_001277990.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.65

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-44373017-C-T is Benign according to our data. Variant chr10-44373017-C-T is described in ClinVar as Benign. ClinVar VariationId is 1233193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277990.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	NM_001277990.2		c.183G>A	p.Leu61Leu	synonymous	Exon 3 of 3	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.*311G>A		3_prime_UTR	Exon 4 of 4	NP_000600.1	P48061-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.*311G>A		3_prime_UTR	Exon 4 of 4	ENSP00000363551.2	P48061-1
	CXCL12	ENST00000395793.7	TSL:5	c.183G>A	p.Leu61Leu	synonymous	Exon 3 of 3	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6922

AN:

152194

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.0371

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.0561

Gnomad SAS

AF:

0.0593

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0333

Gnomad OTH

AF:

0.0368

GnomAD2 exomes

AF:

0.0422

AC:

5774

AN:

136852

AF XY:

0.0425

show subpopulations

Gnomad AFR exome

AF:

0.0692

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.0633

Gnomad FIN exome

AF:

0.0209

Gnomad NFE exome

AF:

0.0335

Gnomad OTH exome

AF:

0.0409

GnomAD4 exome

AF:

0.0345

AC:

47760

AN:

1383726

Hom.:

956

Cov.:

AF XY:

0.0353

AC XY:

24104

AN XY:

682802

show subpopulations

African (AFR)

AF:

0.0706

AC:

2229

AN:

31592

American (AMR)

AF:

0.0453

AC:

1617

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.0158

AC:

399

AN:

25180

East Asian (EAS)

AF:

0.0442

AC:

1578

AN:

35734

South Asian (SAS)

AF:

0.0579

AC:

4587

AN:

79236

European-Finnish (FIN)

AF:

0.0220

AC:

745

AN:

33806

Middle Eastern (MID)

AF:

0.0546

AC:

311

AN:

5696

European-Non Finnish (NFE)

AF:

0.0316

AC:

34087

AN:

1078880

Other (OTH)

AF:

0.0381

AC:

2207

AN:

57904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

2903

5806

8710

11613

14516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1350

2700

4050

5400

6750

<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:

0.0456

AC:

6939

AN:

152312

Hom.:

185

Cov.:

AF XY:

0.0445

AC XY:

3315

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0749

AC:

3113

AN:

41570

American (AMR)

AF:

0.0372

AC:

569

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3468

East Asian (EAS)

AF:

0.0559

AC:

289

AN:

5174

South Asian (SAS)

AF:

0.0600

AC:

289

AN:

4818

European-Finnish (FIN)

AF:

0.0202

AC:

215

AN:

10624

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0333

AC:

2264

AN:

68026

Other (OTH)

AF:

0.0359

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

333

666

998

1331

1664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0357

Hom.:

148

Bravo

AF:

0.0476

Asia WGS

AF:

0.0610

AC:

211

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CXCL12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.30

(source)

DANN

Benign

0.43

PhyloP100

-1.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over