10-44379119-T-C

Variant names:

• chr10-44379119-T-C
• rs2839693
• NM_199168.4:c.180-396A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199168.4(CXCL12):​c.180-396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 151,986 control chromosomes in the GnomAD database, including 53,232 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (53232 hom., cov: 30)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.180-396A>G		intron_variant	Intron 2 of 2	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.180-396A>G		intron_variant	Intron 2 of 2	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126742 AN: 151868 Hom.: 53189 Cov.: 30

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.866

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.835 AC: 126838 AN: 151986 Hom.: 53232 Cov.: 30 AF XY: 0.840 AC XY: 62377 AN XY: 74298

African (AFR) AF: 0.732 AC: 30316 AN: 41406

American (AMR) AF: 0.912 AC: 13949 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2952 AN: 3472

East Asian (EAS) AF: 0.866 AC: 4446 AN: 5134

South Asian (SAS) AF: 0.849 AC: 4064 AN: 4784

European-Finnish (FIN) AF: 0.933 AC: 9886 AN: 10596

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58370 AN: 67988

Other (OTH) AF: 0.868 AC: 1837 AN: 2116

Alfa AF: 0.813 Hom.: 3056

Bravo AF: 0.830

Asia WGS AF: 0.836 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.036
DANN	Benign	0.41
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2839693; hg19: chr10-44874567;