Genetic Variant CXCL12:c.*693T>C (chr10-44372635-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000374429.6(CXCL12):c.*693T>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 0.99 in 1,336,452 control chromosomes in the GnomAD database, including 655,260 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 0.95 ( 69236 hom., cov: 33)

Exomes 𝑓: 0.99 ( 586024 hom. )

Consequence

CXCL12
ENST00000374429.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

Publications

7 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2 link	c.*253T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001264919.1
CXCL12	NM_000609.7 link	c.*693T>C		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6 link	c.*693T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2
CXCL12	ENST00000395793.7 link	c.*253T>C		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000379139.3

Frequencies

GnomAD3 genomes

AF:

0.951

AC:

144687

AN:

152160

Hom.:

69188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.970

GnomAD4 exome

AF:

0.995

AC:

1177664

AN:

1184176

Hom.:

586024

Cov.:

AF XY:

0.995

AC XY:

562819

AN XY:

565654

show subpopulations

African (AFR)

AF:

0.824

AC:

22029

AN:

26720

American (AMR)

AF:

0.987

AC:

12872

AN:

13042

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

16616

AN:

16628

East Asian (EAS)

AF:

1.00

AC:

30393

AN:

30394

South Asian (SAS)

AF:

0.998

AC:

40409

AN:

40486

European-Finnish (FIN)

AF:

1.00

AC:

25506

AN:

25506

Middle Eastern (MID)

AF:

0.984

AC:

3242

AN:

3294

European-Non Finnish (NFE)

AF:

0.999

AC:

978346

AN:

979284

Other (OTH)

AF:

0.988

AC:

48251

AN:

48822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

248

496

745

993

1241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20998

41996

62994

83992

104990

<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:

0.951

AC:

144793

AN:

152276

Hom.:

69236

Cov.:

AF XY:

0.953

AC XY:

70953

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.830

AC:

34458

AN:

41512

American (AMR)

AF:

0.984

AC:

15061

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

3465

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5177

AN:

5178

South Asian (SAS)

AF:

0.997

AC:

4813

AN:

4826

European-Finnish (FIN)

AF:

1.00

AC:

10624

AN:

10624

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67945

AN:

68040

Other (OTH)

AF:

0.970

AC:

2051

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

325

650

976

1301

1626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.970

Hom.:

98581

Bravo

AF:

0.944

Asia WGS

AF:

0.989

AC:

3439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.015

(source)

DANN

Benign

0.52

PhyloP100

-2.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over