10-44373416-C-A

Variant names:

• chr10-44373416-C-A
• rs266090
• ENST00000374429.6:c.267-73G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001277990.2(CXCL12):​c.110-326G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000835 in 1,197,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277990.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	NM_001277990.2		c.110-326G>T		intron	N/A	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.267-73G>T		intron	N/A	NP_000600.1	P48061-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.267-73G>T		intron	N/A	ENSP00000363551.2	P48061-1
	CXCL12	ENST00000395793.7	TSL:5	c.110-326G>T		intron	N/A	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.35e-7 AC: 1 AN: 1197608 Hom.: 0 AF XY: 0.00000166 AC XY: 1 AN XY: 602754

African (AFR) AF: 0.00 AC: 0 AN: 27754

American (AMR) AF: 0.00 AC: 0 AN: 37812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23914

East Asian (EAS) AF: 0.00 AC: 0 AN: 36018

South Asian (SAS) AF: 0.00 AC: 0 AN: 76116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5318

European-Non Finnish (NFE) AF: 0.00000112 AC: 1 AN: 888924

Other (OTH) AF: 0.00 AC: 0 AN: 51364

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.018
DANN	Benign	0.49
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs266090; hg19: chr10-44868864;