Genetic Variant CXCL12:c.*1630T>C (chr10-44371698-A-G) – 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.*1630T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 153,258 control chromosomes in the GnomAD database, including 6,292 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 0.27 ( 6251 hom., cov: 33)

Exomes 𝑓: 0.27 ( 41 hom. )

Consequence

CXCL12
ENST00000374429.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.638

Publications

26 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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2 link	c.*1190T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001264919.1	P48061-7
CXCL12	NM_000609.7 link	c.*1630T>C		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1	P48061-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6 link	c.*1630T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2		P48061-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41313

AN:

152076

Hom.:

6248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.267

AC:

284

AN:

1064

Hom.:

Cov.:

AF XY:

0.254

AC XY:

159

AN XY:

626

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.300

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.185

AC:

AN:

184

European-Finnish (FIN)

AF:

0.342

AC:

AN:

114

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.279

AC:

181

AN:

648

Other (OTH)

AF:

0.280

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.272

AC:

41333

AN:

152194

Hom.:

6251

Cov.:

AF XY:

0.277

AC XY:

20620

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.160

AC:

6660

AN:

41534

American (AMR)

AF:

0.428

AC:

6537

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

864

AN:

3470

East Asian (EAS)

AF:

0.194

AC:

1007

AN:

5186

South Asian (SAS)

AF:

0.282

AC:

1358

AN:

4824

European-Finnish (FIN)

AF:

0.362

AC:

3836

AN:

10586

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20072

AN:

68000

Other (OTH)

AF:

0.285

AC:

603

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1524

3048

4573

6097

7621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.297

Hom.:

11604

Bravo

AF:

0.275

Asia WGS

AF:

0.240

AC:

832

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.29

(source)

DANN

Benign

0.46

PhyloP100

-0.64

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