Genetic Variant CXCL12:c.*2501A>T (chr10-44370827-T-A) – 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.*2501A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,440 control chromosomes in the GnomAD database, including 152 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 0.039 ( 152 hom., cov: 33)

Exomes 𝑓: 0.057 ( 0 hom. )

Consequence

CXCL12
ENST00000374429.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

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=-0.62).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374429.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	NM_001277990.2		c.*2061A>T		3_prime_UTR	Exon 3 of 3	NP_001264919.1
	CXCL12	NM_000609.7		c.*2501A>T		3_prime_UTR	Exon 4 of 4	NP_000600.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.*2501A>T		3_prime_UTR	Exon 4 of 4	ENSP00000363551.2

Frequencies

GnomAD3 genomes

AF:

0.0395

AC:

6006

AN:

152200

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0303

Gnomad ASJ

AF:

0.0795

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0981

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0489

Gnomad OTH

AF:

0.0359

GnomAD4 exome

AF:

0.0574

AC:

AN:

122

Hom.:

Cov.:

AF XY:

0.0510

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0588

AC:

AN:

102

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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

AF:

0.0394

AC:

6007

AN:

152318

Hom.:

152

Cov.:

AF XY:

0.0395

AC XY:

2945

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0221

AC:

918

AN:

41574

American (AMR)

AF:

0.0302

AC:

462

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0795

AC:

276

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0986

AC:

476

AN:

4828

European-Finnish (FIN)

AF:

0.0386

AC:

410

AN:

10614

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0489

AC:

3325

AN:

68022

Other (OTH)

AF:

0.0355

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

309

618

928

1237

1546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0462

Hom.:

Bravo

AF:

0.0346

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over