Variant 10-44375898-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
CXCL12	NM_001033886.2 linkuse as main transcript	c.*41C>T	3_prime_UTR_variant	4/4	NP_001029058.1
CXCL12	NM_000609.7 linkuse as main transcript	c.267-2555C>T	intron_variant		NP_000600.1
CXCL12	NM_001277990.2 linkuse as main transcript	c.110-2808C>T	intron_variant		NP_001264919.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris	UniProt
CXCL12	ENST00000374426.6 linkuse as main transcript	c.*41C>T	3_prime_UTR_variant	4/4	1	ENSP00000363548		P48061-3
CXCL12	ENST00000374429.6 linkuse as main transcript	c.267-2555C>T	intron_variant		1	ENSP00000363551	A1	P48061-1
CXCL12	ENST00000395793.7 linkuse as main transcript	c.110-2808C>T	intron_variant		5	ENSP00000379139		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

GnomAD3 exomes

AF:

0.0832

AC:

20634

AN:

247902

Hom.:

959

AF XY:

0.0837

AC XY:

11210

AN XY:

133998

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 SAS exome

AF:

0.0660

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

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.0872

Gnomad4 ASJ exome

AF:

0.0675

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.0680

Gnomad4 FIN exome

AF:

0.0766

Gnomad4 NFE exome

AF:

0.0987

Gnomad4 OTH exome

AF:

0.0866

GnomAD4 genome

AF:

0.0702

AC:

10690

AN:

152256

Hom.:

470

Cov.:

AF XY:

0.0699

AC XY:

5200

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.0819

Gnomad4 ASJ

AF:

0.0681

Gnomad4 EAS

AF:

0.0941

Gnomad4 SAS

AF:

0.0664

Gnomad4 FIN

AF:

0.0774

Gnomad4 NFE

AF:

0.0957

Gnomad4 OTH

AF:

0.0909

Alfa

AF:

0.0943

Hom.:

699

Bravo

AF:

0.0698

Asia WGS

AF:

0.0620

AC:

216

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.85

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