Genetic Variant CXCL12:c.*1007G>C (chr10-44372321-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001277990.2(CXCL12):c.*567G>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 0.226 in 155,600 control chromosomes in the GnomAD database, including 4,860 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 0.23 ( 4716 hom., cov: 33)

Exomes 𝑓: 0.26 ( 144 hom. )

Consequence

CXCL12
NM_001277990.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.398

Publications

15 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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 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.*567G>C		3_prime_UTR	Exon 3 of 3	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.*1007G>C		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.*1007G>C		3_prime_UTR	Exon 4 of 4	ENSP00000363551.2	P48061-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34338

AN:

152056

Hom.:

4715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0856

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.260

AC:

890

AN:

3426

Hom.:

144

Cov.:

AF XY:

0.257

AC XY:

453

AN XY:

1760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.376

AC:

320

AN:

852

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

AN:

East Asian (EAS)

AF:

0.0208

AC:

AN:

South Asian (SAS)

AF:

0.229

AC:

AN:

210

European-Finnish (FIN)

AF:

0.214

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

474

AN:

2108

Other (OTH)

AF:

0.263

AC:

AN:

156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.226

AC:

34341

AN:

152174

Hom.:

4716

Cov.:

AF XY:

0.232

AC XY:

17271

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0854

AC:

3549

AN:

41552

American (AMR)

AF:

0.390

AC:

5964

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

812

AN:

3472

East Asian (EAS)

AF:

0.136

AC:

702

AN:

5172

South Asian (SAS)

AF:

0.219

AC:

1055

AN:

4818

European-Finnish (FIN)

AF:

0.342

AC:

3613

AN:

10566

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17793

AN:

67988

Other (OTH)

AF:

0.250

AC:

528

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1283

2567

3850

5134

6417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.154

Hom.:

343

Bravo

AF:

0.227

Asia WGS

AF:

0.178

AC:

618

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.7

(source)

DANN

Benign

0.34

PhyloP100

-0.40

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