Variant 10-44377752-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000395794.2(CXCL12):c.420G>T(p.Val140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00596 in 1,598,366 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 40 hom. )

Consequence

CXCL12
ENST00000395794.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.101

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 -17 ACMG points.

BP4

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

BP6

Variant 10-44377752-C-A is Benign according to our data. Variant chr10-44377752-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.101 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_199168.4 linkuse as main transcript	c.*881G>T		3_prime_UTR_variant	3/3	ENST00000343575.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000343575.11 linkuse as main transcript	c.*881G>T		3_prime_UTR_variant	3/3	1	NM_199168.4	P4	P48061-2

Frequencies

GnomAD3 genomes

AF:

0.00516

AC:

785

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00620

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00557

AC:

1288

AN:

231434

Hom.:

AF XY:

0.00541

AC XY:

691

AN XY:

127738

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.00213

Gnomad ASJ exome

AF:

0.0404

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000991

Gnomad FIN exome

AF:

0.00206

Gnomad NFE exome

AF:

0.00673

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00605

AC:

8748

AN:

1446024

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

4282

AN XY:

719716

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.0416

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00268

Gnomad4 NFE exome

AF:

0.00627

Gnomad4 OTH exome

AF:

0.00703

GnomAD4 genome

AF:

0.00515

AC:

784

AN:

152342

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

362

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.0507

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00619

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00654

Hom.:

Bravo

AF:

0.00530

EpiCase

AF:

0.00649

EpiControl

AF:

0.00718

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CXCL12-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

CXCL12: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

DANN

Benign

0.49

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.

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