Genetic Variant ENST00000374429:c.*232A>G (chr10-44373096-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The ENST00000374429(CXCL12):c.*232A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,536,422 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 7 hom. )

Consequence

CXCL12
ENST00000374429 3_prime_UTR

Scores

Splicing: ADA: 0.00003135

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.397

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 10-44373096-T-C is Benign according to our data. Variant chr10-44373096-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3037442.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_000609.7 link	c.*232A>G		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1	P48061-1
CXCL12	NM_001277990.2 link	c.110-6A>G		splice_region_variant, intron_variant	Intron 2 of 2		NP_001264919.1	P48061-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429 link	c.*232A>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2		P48061-1
CXCL12	ENST00000395793.7 link	c.110-6A>G		splice_region_variant, intron_variant	Intron 2 of 2	5		ENSP00000379139.3		P48061-7

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

358

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00394

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00222

AC:

310

AN:

139700

Hom.:

AF XY:

0.00242

AC XY:

182

AN XY:

75314

show subpopulations

Gnomad AFR exome

AF:

0.000427

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.000604

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000800

Gnomad FIN exome

AF:

0.000616

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00337

GnomAD4 exome

AF:

0.00301

AC:

4161

AN:

1384054

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

2065

AN XY:

682800

show subpopulations

Gnomad4 AFR exome

AF:

0.000349

Gnomad4 AMR exome

AF:

0.00167

Gnomad4 ASJ exome

AF:

0.000678

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.000587

Gnomad4 NFE exome

AF:

0.00355

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00235

AC:

358

AN:

152368

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00394

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CXCL12-related disorder

Benign:1

Feb 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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

-0.42

CADD

Benign

9.1

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.012

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