Genetic Variant ENST00000374429.6:c.*2148C>T (chr10-44371180-G-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.*2148C>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 0.0436 in 248,208 control chromosomes in the GnomAD database, including 267 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 0.046 ( 185 hom., cov: 33)

Exomes 𝑓: 0.041 ( 82 hom. )

Consequence

CXCL12
ENST00000374429.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.364

Publications

5 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2 link	c.*1708C>T		3_prime_UTR_variant	Exon 3 of 3		NP_001264919.1	P48061-7
CXCL12	NM_000609.7 link	c.*2148C>T		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1	P48061-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6 link	c.*2148C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2		P48061-1

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6921

AN:

152224

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0745

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0370

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.0562

Gnomad SAS

AF:

0.0604

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0333

Gnomad OTH

AF:

0.0368

GnomAD4 exome

AF:

0.0406

AC:

3890

AN:

95866

Hom.:

Cov.:

AF XY:

0.0424

AC XY:

2346

AN XY:

55358

show subpopulations

African (AFR)

AF:

0.0813

AC:

AN:

1168

American (AMR)

AF:

0.0454

AC:

AN:

1828

Ashkenazi Jewish (ASJ)

AF:

0.0128

AC:

AN:

2104

East Asian (EAS)

AF:

0.0574

AC:

AN:

1672

South Asian (SAS)

AF:

0.0601

AC:

1374

AN:

22876

European-Finnish (FIN)

AF:

0.0210

AC:

121

AN:

5764

Middle Eastern (MID)

AF:

0.0496

AC:

AN:

524

European-Non Finnish (NFE)

AF:

0.0340

AC:

1882

AN:

55282

Other (OTH)

AF:

0.0400

AC:

186

AN:

4648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

174

348

523

697

871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0455

AC:

6935

AN:

152342

Hom.:

185

Cov.:

AF XY:

0.0446

AC XY:

3320

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0746

AC:

3102

AN:

41574

American (AMR)

AF:

0.0371

AC:

568

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3468

East Asian (EAS)

AF:

0.0559

AC:

290

AN:

5188

South Asian (SAS)

AF:

0.0611

AC:

295

AN:

4828

European-Finnish (FIN)

AF:

0.0203

AC:

216

AN:

10628

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0333

AC:

2265

AN:

68030

Other (OTH)

AF:

0.0360

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

346

692

1037

1383

1729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0369

Hom.:

152

Bravo

AF:

0.0475

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.2

(source)

DANN

Benign

0.64

PhyloP100

0.36

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