10-44377749-T-C

Variant names:

• chr10-44377749-T-C
• rs183966906
• ENST00000395794.2:c.423A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001178134.2(CXCL12):​c.423A>G​(p.Ter141Ter) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (16 hom.)
• Consequence: CXCL12 NM_001178134.2 stop_retained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.242

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: 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 no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.242 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.*884A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575	c.*884A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152198 Hom.: 1 Cov.: 33

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

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

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 AF: 0.00256 AC: 390 AN: 152316 Hom.: 1 Cov.: 33 AF XY: 0.00242 AC XY: 180 AN XY: 74484

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: no assertion criteria provided

Submissions by phenotype

CXCL12-related disorder Benign:1

Oct 18, 2022

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	-0.88
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

Other links and lift over

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