Genetic Variant CXCL12:c.-15_-4delCCGCCCGCCCGC (chr10-44385008-CGCGGGCGGGCGG-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_199168.4(CXCL12):c.-15_-4delCCGCCCGCCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 410,968 control chromosomes in the GnomAD database, including 2 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00038 ( 2 hom. )

Consequence

CXCL12
NM_199168.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.28

Publications

0 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:

ENSG00000303087 (HGNC:):

ENSG00000303087 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199168.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CXCL12	NM_199168.4	MANE Select	c.-15_-4delCCGCCCGCCCGC	5_prime_UTR	Exon 1 of 3	NP_954637.1	P48061-2
CXCL12	NM_001178134.2		c.-15_-4delCCGCCCGCCCGC	5_prime_UTR	Exon 1 of 4	NP_001171605.1	P48061-4
CXCL12	NM_001033886.2		c.-15_-4delCCGCCCGCCCGC	5_prime_UTR	Exon 1 of 4	NP_001029058.1	P48061-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.-15_-4delCCGCCCGCCCGC	5_prime_UTR	Exon 1 of 3	ENSP00000339913.6	P48061-2
CXCL12	ENST00000395794.2	TSL:1	c.-15_-4delCCGCCCGCCCGC	5_prime_UTR	Exon 1 of 4	ENSP00000379140.2	P48061-4
CXCL12	ENST00000374426.6	TSL:1	c.-15_-4delCCGCCCGCCCGC	5_prime_UTR	Exon 1 of 4	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes

AF:

0.000176

AC:

AN:

119512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000518

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000874

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000184

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000347

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000263

AC:

AN:

57116

AF XY:

0.000266

show subpopulations

Gnomad AFR exome

AF:

0.00325

Gnomad AMR exome

AF:

0.000254

Gnomad ASJ exome

AF:

0.000204

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000583

Gnomad NFE exome

AF:

0.0000845

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000384

AC:

112

AN:

291456

Hom.:

AF XY:

0.000345

AC XY:

AN XY:

159454

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

7710

American (AMR)

AF:

0.000363

AC:

AN:

13778

Ashkenazi Jewish (ASJ)

AF:

0.000226

AC:

AN:

8842

East Asian (EAS)

AF:

0.000937

AC:

AN:

3202

South Asian (SAS)

AF:

0.000411

AC:

AN:

41366

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1102

European-Non Finnish (NFE)

AF:

0.000327

AC:

AN:

192764

Other (OTH)

AF:

0.000314

AC:

AN:

12750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

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:

0.000176

AC:

AN:

119512

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

AN XY:

57134

show subpopulations

African (AFR)

AF:

0.000518

AC:

AN:

32836

American (AMR)

AF:

0.0000874

AC:

AN:

11446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3100

East Asian (EAS)

AF:

0.00

AC:

AN:

3416

South Asian (SAS)

AF:

0.00

AC:

AN:

3064

European-Finnish (FIN)

AF:

0.000184

AC:

AN:

5434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000347

AC:

AN:

57556

Other (OTH)

AF:

0.00

AC:

AN:

1626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.599

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=299/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-44385008-CGCGGGCGGGCGGGCGG-CGCGG

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