Genetic Variant CXCL12:c.-11_-4delCCGCCCGC (chr10-44385008-CGCGGGCGG-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_199168.4(CXCL12):c.-11_-4delCCGCCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 409,864 control chromosomes in the GnomAD database, including 43 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0036 ( 43 hom. )

Consequence

CXCL12
NM_199168.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -6 ACMG points.

BP6

Variant 10-44385008-CGCGGGCGG-C is Benign according to our data. Variant chr10-44385008-CGCGGGCGG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2640422.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 43 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.-11_-4delCCGCCCGC	5_prime_UTR	Exon 1 of 3	NP_954637.1	P48061-2
CXCL12	NM_001178134.2		c.-11_-4delCCGCCCGC	5_prime_UTR	Exon 1 of 4	NP_001171605.1	P48061-4
CXCL12	NM_001033886.2		c.-11_-4delCCGCCCGC	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.-11_-4delCCGCCCGC	5_prime_UTR	Exon 1 of 3	ENSP00000339913.6	P48061-2
CXCL12	ENST00000395794.2	TSL:1	c.-11_-4delCCGCCCGC	5_prime_UTR	Exon 1 of 4	ENSP00000379140.2	P48061-4
CXCL12	ENST00000374426.6	TSL:1	c.-11_-4delCCGCCCGC	5_prime_UTR	Exon 1 of 4	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes

AF:

0.000937

AC:

112

AN:

119518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000961

Gnomad ASJ

AF:

0.0223

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000278

Gnomad OTH

AF:

0.00246

GnomAD2 exomes

AF:

0.00284

AC:

162

AN:

57116

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.00325

Gnomad AMR exome

AF:

0.00305

Gnomad ASJ exome

AF:

0.0214

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000292

Gnomad NFE exome

AF:

0.000803

Gnomad OTH exome

AF:

0.00192

GnomAD4 exome

AF:

0.00363

AC:

1055

AN:

290314

Hom.:

AF XY:

0.00323

AC XY:

514

AN XY:

158922

show subpopulations

African (AFR)

AF:

0.00365

AC:

AN:

7676

American (AMR)

AF:

0.00357

AC:

AN:

13732

Ashkenazi Jewish (ASJ)

AF:

0.0435

AC:

384

AN:

8828

East Asian (EAS)

AF:

0.00

AC:

AN:

3188

South Asian (SAS)

AF:

0.000436

AC:

AN:

41264

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

9912

Middle Eastern (MID)

AF:

0.00366

AC:

AN:

1094

European-Non Finnish (NFE)

AF:

0.00249

AC:

478

AN:

191906

Other (OTH)

AF:

0.00731

AC:

AN:

12714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.000954

AC:

114

AN:

119550

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

57164

show subpopulations

African (AFR)

AF:

0.000426

AC:

AN:

32870

American (AMR)

AF:

0.000959

AC:

AN:

11470

Ashkenazi Jewish (ASJ)

AF:

0.0223

AC:

AN:

3100

East Asian (EAS)

AF:

0.00

AC:

AN:

3408

South Asian (SAS)

AF:

0.00

AC:

AN:

3066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.000278

AC:

AN:

57556

Other (OTH)

AF:

0.00244

AC:

AN:

1640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=300/0

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-CGCGGGCGG

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