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10-44377749-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000395794.2(CXCL12):c.423A>G(p.Ter141=) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,598,376 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0036 ( 16 hom. )

Consequence

CXCL12
ENST00000395794.2 stop_retained

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.242
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-44377749-T-C is Benign according to our data. Variant chr10-44377749-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044678.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.242 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CXCL12NM_199168.4 linkuse as main transcriptc.*884A>G 3_prime_UTR_variant 3/3 ENST00000343575.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CXCL12ENST00000343575.11 linkuse as main transcriptc.*884A>G 3_prime_UTR_variant 3/31 NM_199168.4 P4P48061-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00256
AC:
390
AN:
152198
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00772
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00388
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00311
AC:
720
AN:
231450
Hom.:
2
AF XY:
0.00297
AC XY:
380
AN XY:
127742
show subpopulations
Gnomad AFR exome
AF:
0.000935
Gnomad AMR exome
AF:
0.00105
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00652
Gnomad NFE exome
AF:
0.00534
Gnomad OTH exome
AF:
0.00290
GnomAD4 exome
AF:
0.00361
AC:
5219
AN:
1446060
Hom.:
16
Cov.:
32
AF XY:
0.00338
AC XY:
2433
AN XY:
719736
show subpopulations
Gnomad4 AFR exome
AF:
0.000597
Gnomad4 AMR exome
AF:
0.000939
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00884
Gnomad4 NFE exome
AF:
0.00414
Gnomad4 OTH exome
AF:
0.00352
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00256
AC:
390
AN:
152316
Hom.:
1
Cov.:
33
AF XY:
0.00242
AC XY:
180
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00772
Gnomad4 NFE
AF:
0.00388
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00255
Hom.:
1
Bravo
AF:
0.00208
EpiCase
AF:
0.00371
EpiControl
AF:
0.00296

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CXCL12-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 18, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.84
Dann
Benign
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs183966906; hg19: chr10-44873197; COSMIC: COSV59107350; COSMIC: COSV59107350; API