Genetic Variant CXCL12:c.-7_-4dupCCGC (chr10-44385008-C-CGCGG) – 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.-7_-4dupCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 412,500 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0058 ( 1 hom., cov: 28)

Exomes 𝑓: 0.0036 ( 2 hom. )

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:

Genome browser will be placed here

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4 link	c.-7_-4dupCCGC		5_prime_UTR_variant	Exon 1 of 3	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11 link	c.-7_-4dupCCGC		5_prime_UTR_variant	Exon 1 of 3	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

697

AN:

119510

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00904

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00294

Gnomad FIN

AF:

0.000184

Gnomad MID

AF:

0.00368

Gnomad NFE

AF:

0.00313

Gnomad OTH

AF:

0.00677

GnomAD2 exomes

AF:

0.00137

AC:

AN:

57116

AF XY:

0.00142

show subpopulations

Gnomad AFR exome

AF:

0.00325

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00611

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.00357

AC:

1045

AN:

292958

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

591

AN XY:

160248

show subpopulations

African (AFR)

AF:

0.0110

AC:

AN:

7742

American (AMR)

AF:

0.00152

AC:

AN:

13854

Ashkenazi Jewish (ASJ)

AF:

0.0148

AC:

131

AN:

8868

East Asian (EAS)

AF:

0.000935

AC:

AN:

3210

South Asian (SAS)

AF:

0.00101

AC:

AN:

41460

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

9954

Middle Eastern (MID)

AF:

0.00454

AC:

AN:

1102

European-Non Finnish (NFE)

AF:

0.00343

AC:

665

AN:

193976

Other (OTH)

AF:

0.00610

AC:

AN:

12792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00581

AC:

695

AN:

119542

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

307

AN XY:

57158

show subpopulations

African (AFR)

AF:

0.0129

AC:

423

AN:

32862

American (AMR)

AF:

0.00366

AC:

AN:

11470

Ashkenazi Jewish (ASJ)

AF:

0.00904

AC:

AN:

3098

East Asian (EAS)

AF:

0.00

AC:

AN:

3408

South Asian (SAS)

AF:

0.00294

AC:

AN:

3066

European-Finnish (FIN)

AF:

0.000184

AC:

AN:

5434

Middle Eastern (MID)

AF:

0.00407

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.00313

AC:

180

AN:

57556

Other (OTH)

AF:

0.00671

AC:

AN:

1640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

118

148

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:

0.0000563

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.69

Mutation Taster

=299/1

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGGGCGGGCGG

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