Variant 10-44373017-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000374429.6(CXCL12):c.*311G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,536,038 control chromosomes in the GnomAD database, including 1,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 185 hom., cov: 33)

Exomes 𝑓: 0.035 ( 956 hom. )

Consequence

CXCL12
ENST00000374429.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.65

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-44373017-C-T is Benign according to our data. Variant chr10-44373017-C-T is described in ClinVar as [Benign]. Clinvar id is 1233193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_001277990.2 linkuse as main transcript	c.183G>A	p.Leu61=	synonymous_variant	3/3		NP_001264919.1
CXCL12	NM_000609.7 linkuse as main transcript	c.*311G>A		3_prime_UTR_variant	4/4		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6 linkuse as main transcript	c.*311G>A		3_prime_UTR_variant	4/4	1		ENSP00000363551	A1	P48061-1
CXCL12	ENST00000395793.7 linkuse as main transcript	c.183G>A	p.Leu61=	synonymous_variant	3/3	5		ENSP00000379139		P48061-7

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6922

AN:

152194

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.0371

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.0561

Gnomad SAS

AF:

0.0593

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0333

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0422

AC:

5774

AN:

136852

Hom.:

164

AF XY:

0.0425

AC XY:

3163

AN XY:

74366

show subpopulations

Gnomad AFR exome

AF:

0.0692

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.0633

Gnomad SAS exome

AF:

0.0557

Gnomad FIN exome

AF:

0.0209

Gnomad NFE exome

AF:

0.0335

Gnomad OTH exome

AF:

0.0409

GnomAD4 exome

AF:

0.0345

AC:

47760

AN:

1383726

Hom.:

956

Cov.:

AF XY:

0.0353

AC XY:

24104

AN XY:

682802

show subpopulations

Gnomad4 AFR exome

AF:

0.0706

Gnomad4 AMR exome

AF:

0.0453

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.0442

Gnomad4 SAS exome

AF:

0.0579

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0316

Gnomad4 OTH exome

AF:

0.0381

GnomAD4 genome

AF:

0.0456

AC:

6939

AN:

152312

Hom.:

185

Cov.:

AF XY:

0.0445

AC XY:

3315

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0749

Gnomad4 AMR

AF:

0.0372

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.0559

Gnomad4 SAS

AF:

0.0600

Gnomad4 FIN

AF:

0.0202

Gnomad4 NFE

AF:

0.0333

Gnomad4 OTH

AF:

0.0359

Alfa

AF:

0.0329

Hom.:

104

Bravo

AF:

0.0476

Asia WGS

AF:

0.0610

AC:

211

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CXCL12-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2020

This variant is classified as 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

-0.83

CADD

Benign

0.30

DANN

Benign

0.43

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over