Genetic Variant ENST00000374426.6:c.*41C>T (chr10-44375898-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000374426.6(CXCL12):c.*41C>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 0.0906 in 1,607,966 control chromosomes in the GnomAD database, including 7,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 470 hom., cov: 33)

Exomes 𝑓: 0.093 ( 6596 hom. )

Consequence

CXCL12
ENST00000374426.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.340

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 10-44375898-G-A is Benign according to our data. Variant chr10-44375898-G-A is described in ClinVar as Benign. ClinVar VariationId is 1220639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374426.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
CXCL12	NM_001033886.2	c.*41C>T	3_prime_UTR	Exon 4 of 4	NP_001029058.1	P48061-3
CXCL12	NM_001277990.2	c.110-2808C>T	intron	N/A	NP_001264919.1	P48061-7
CXCL12	NM_000609.7	c.267-2555C>T	intron	N/A	NP_000600.1	P48061-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CXCL12	ENST00000374426.6	TSL:1	c.*41C>T	3_prime_UTR	Exon 4 of 4	ENSP00000363548.2	P48061-3
CXCL12	ENST00000374429.6	TSL:1	c.267-2555C>T	intron	N/A	ENSP00000363551.2	P48061-1
CXCL12	ENST00000395793.7	TSL:5	c.110-2808C>T	intron	N/A	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes

AF:

0.0703

AC:

10697

AN:

152138

Hom.:

471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0821

Gnomad ASJ

AF:

0.0681

Gnomad EAS

AF:

0.0939

Gnomad SAS

AF:

0.0672

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0957

Gnomad OTH

AF:

0.0919

GnomAD2 exomes

AF:

0.0832

AC:

20634

AN:

247902

AF XY:

0.0837

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.0858

Gnomad ASJ exome

AF:

0.0683

Gnomad EAS exome

AF:

0.0945

Gnomad FIN exome

AF:

0.0783

Gnomad NFE exome

AF:

0.0966

Gnomad OTH exome

AF:

0.0920

GnomAD4 exome

AF:

0.0928

AC:

135069

AN:

1455710

Hom.:

6596

Cov.:

AF XY:

0.0920

AC XY:

66609

AN XY:

724134

show subpopulations

African (AFR)

AF:

0.0148

AC:

487

AN:

32836

American (AMR)

AF:

0.0872

AC:

3807

AN:

43664

Ashkenazi Jewish (ASJ)

AF:

0.0675

AC:

1755

AN:

25988

East Asian (EAS)

AF:

0.101

AC:

4015

AN:

39678

South Asian (SAS)

AF:

0.0680

AC:

5796

AN:

85184

European-Finnish (FIN)

AF:

0.0766

AC:

4088

AN:

53362

Middle Eastern (MID)

AF:

0.0696

AC:

288

AN:

4140

European-Non Finnish (NFE)

AF:

0.0987

AC:

109643

AN:

1110898

Other (OTH)

AF:

0.0866

AC:

5190

AN:

59960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

6433

12867

19300

25734

32167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4050

8100

12150

16200

20250

<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:

0.0702

AC:

10690

AN:

152256

Hom.:

470

Cov.:

AF XY:

0.0699

AC XY:

5200

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0195

AC:

812

AN:

41562

American (AMR)

AF:

0.0819

AC:

1254

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0681

AC:

236

AN:

3466

East Asian (EAS)

AF:

0.0941

AC:

486

AN:

5162

South Asian (SAS)

AF:

0.0664

AC:

320

AN:

4818

European-Finnish (FIN)

AF:

0.0774

AC:

821

AN:

10610

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0957

AC:

6511

AN:

68014

Other (OTH)

AF:

0.0909

AC:

192

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

510

1020

1529

2039

2549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0906

Hom.:

870

Bravo

AF:

0.0698

Asia WGS

AF:

0.0620

AC:

216

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.34

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