Genetic Variant CXCL12:c.-11_-4dupCCGCCCGC (chr10-44385008-C-CGCGGGCGG) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_199168.4(CXCL12):c.-11_-4dupCCGCCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 293,022 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000044 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CXCL12
NM_199168.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.689

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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
CXCL12	NM_199168.4	MANE Select	c.-11_-4dupCCGCCCGC	5_prime_UTR	Exon 1 of 3	NP_954637.1
CXCL12	NM_001178134.2		c.-11_-4dupCCGCCCGC	5_prime_UTR	Exon 1 of 4	NP_001171605.1
CXCL12	NM_001033886.2		c.-11_-4dupCCGCCCGC	5_prime_UTR	Exon 1 of 4	NP_001029058.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

119524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000368

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000139

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000444

AC:

AN:

293022

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

160284

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

7746

American (AMR)

AF:

0.00

AC:

AN:

13858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8876

East Asian (EAS)

AF:

0.000312

AC:

AN:

3210

South Asian (SAS)

AF:

0.00

AC:

AN:

41470

European-Finnish (FIN)

AF:

0.000100

AC:

AN:

9954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1102

European-Non Finnish (NFE)

AF:

0.0000464

AC:

AN:

194004

Other (OTH)

AF:

0.0000781

AC:

AN:

12802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000920

AC:

AN:

119524

Hom.:

Cov.:

AF XY:

0.0000350

AC XY:

AN XY:

57140

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32840

American (AMR)

AF:

0.00

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:

3066

European-Finnish (FIN)

AF:

0.000368

AC:

AN:

5434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000139

AC:

AN:

57562

Other (OTH)

AF:

0.00

AC:

AN:

1626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

0.69

Splicing

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

Publications

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10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGGGCGG

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