dbSNP rs10793538: CXCL12:c.62-258A>T (chr10-44381138-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_199168.4(CXCL12):c.62-258A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 151,960 control chromosomes in the GnomAD database, including 63,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.91 ( 63091 hom., cov: 32)

Consequence

CXCL12
NM_199168.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0970

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-44381138-T-A is Benign according to our data. Variant chr10-44381138-T-A is described in ClinVar as Benign. ClinVar VariationId is 1181019.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4 link	c.62-258A>T		intron_variant	Intron 1 of 2	ENST00000343575.11	NP_954637.1	P48061-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11 link	c.62-258A>T		intron_variant	Intron 1 of 2	1	NM_199168.4	ENSP00000339913.6		P48061-2

Frequencies

GnomAD3 genomes

AF:

0.907

AC:

137745

AN:

151842

Hom.:

63054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.760

Gnomad AMI

AF:

0.931

Gnomad AMR

AF:

0.947

Gnomad ASJ

AF:

0.985

Gnomad EAS

AF:

0.943

Gnomad SAS

AF:

0.939

Gnomad FIN

AF:

0.980

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.966

Gnomad OTH

AF:

0.933

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.907

AC:

137841

AN:

151960

Hom.:

63091

Cov.:

AF XY:

0.910

AC XY:

67572

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.760

AC:

31428

AN:

41354

American (AMR)

AF:

0.946

AC:

14473

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.985

AC:

3419

AN:

3470

East Asian (EAS)

AF:

0.944

AC:

4866

AN:

5156

South Asian (SAS)

AF:

0.938

AC:

4514

AN:

4810

European-Finnish (FIN)

AF:

0.980

AC:

10381

AN:

10596

Middle Eastern (MID)

AF:

0.959

AC:

280

AN:

292

European-Non Finnish (NFE)

AF:

0.966

AC:

65662

AN:

67970

Other (OTH)

AF:

0.934

AC:

1969

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

605

1209

1814

2418

3023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.933

Hom.:

7762

Bravo

AF:

0.898

Asia WGS

AF:

0.930

AC:

3235

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.1

(source)

DANN

Benign

0.86

PhyloP100

0.097

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over