10-44378805-C-G

Variant names:

• chr10-44378805-C-G
• rs266085
• NM_199168.4:c.180-82G>C

Variant summary

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

The NM_199168.4(CXCL12):​c.180-82G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000815 in 1,226,962 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: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 17 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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199168.4. 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_199168.4	MANE Select	c.180-82G>C		intron	N/A	NP_954637.1	P48061-2
	CXCL12	NM_001178134.2		c.180-82G>C		intron	N/A	NP_001171605.1	P48061-4
	CXCL12	NM_001033886.2		c.180-82G>C		intron	N/A	NP_001029058.1	P48061-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.180-82G>C		intron	N/A	ENSP00000339913.6	P48061-2
	CXCL12	ENST00000395794.2	TSL:1	c.180-82G>C		intron	N/A	ENSP00000379140.2	P48061-4
	CXCL12	ENST00000374426.6	TSL:1	c.180-82G>C		intron	N/A	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.15e-7 AC: 1 AN: 1226962 Hom.: 0 AF XY: 0.00000161 AC XY: 1 AN XY: 621404

African (AFR) AF: 0.00 AC: 0 AN: 28876

American (AMR) AF: 0.00 AC: 0 AN: 43958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24608

East Asian (EAS) AF: 0.00 AC: 0 AN: 38454

South Asian (SAS) AF: 0.00 AC: 0 AN: 81324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4790

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 901028

Other (OTH) AF: 0.00 AC: 0 AN: 52482

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.74
PhyloP100		-0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs266085; hg19: chr10-44874253;