Genetic Variant CXCL12:c.*519G>A (chr10-44372809-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000374429.6(CXCL12):c.*519G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,472,396 control chromosomes in the GnomAD database, including 28,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2405 hom., cov: 32)

Exomes 𝑓: 0.19 ( 25890 hom. )

Consequence

CXCL12
ENST00000374429.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.813

Publications

260 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-44372809-C-T is Benign according to our data. Variant chr10-44372809-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2 link	c.*79G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001264919.1
CXCL12	NM_000609.7 link	c.*519G>A		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6 link	c.*519G>A		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2
CXCL12	ENST00000395793.7 link	c.*79G>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000379139.3

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24815

AN:

152020

Hom.:

2395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.183

GnomAD4 exome

AF:

0.195

AC:

257184

AN:

1320258

Hom.:

25890

Cov.:

AF XY:

0.196

AC XY:

126557

AN XY:

644322

show subpopulations

African (AFR)

AF:

0.0567

AC:

1679

AN:

29618

American (AMR)

AF:

0.170

AC:

4643

AN:

27332

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

4686

AN:

20854

East Asian (EAS)

AF:

0.300

AC:

10544

AN:

35202

South Asian (SAS)

AF:

0.223

AC:

15176

AN:

68188

European-Finnish (FIN)

AF:

0.197

AC:

6208

AN:

31522

Middle Eastern (MID)

AF:

0.285

AC:

1095

AN:

3848

European-Non Finnish (NFE)

AF:

0.193

AC:

201977

AN:

1048754

Other (OTH)

AF:

0.203

AC:

11176

AN:

54940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

12077

24153

36230

48306

60383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7302

14604

21906

29208

36510

<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:

0.163

AC:

24838

AN:

152138

Hom.:

2405

Cov.:

AF XY:

0.165

AC XY:

12275

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0621

AC:

2580

AN:

41520

American (AMR)

AF:

0.173

AC:

2641

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

810

AN:

3472

East Asian (EAS)

AF:

0.270

AC:

1384

AN:

5132

South Asian (SAS)

AF:

0.232

AC:

1116

AN:

4820

European-Finnish (FIN)

AF:

0.187

AC:

1987

AN:

10606

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13627

AN:

67980

Other (OTH)

AF:

0.191

AC:

404

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1070

2140

3209

4279

5349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.183

Hom.:

1713

Bravo

AF:

0.157

Asia WGS

AF:

0.237

AC:

824

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23325742, 19601773, 16306115, 22962615, 24361877, 23615182, 18928397, 9430590, 27832196) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.013

(source)

DANN

Benign

0.31

PhyloP100

-0.81

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over