rs2236534

Variant names:

• chr10-44378861-G-C
• rs2236534
• NM_199168.4:c.180-138C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-44378861-G-C
• chr10-44378861-G-T

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.180-138C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 645,856 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: 0.0000093 (0 hom.)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985
• Publications: 9 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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.180-138C>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.180-138C>G		intron_variant	Intron 2 of 2	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000929 AC: 6 AN: 645856 Hom.: 0 AF XY: 0.00000587 AC XY: 2 AN XY: 340580

African (AFR) AF: 0.00 AC: 0 AN: 17330

American (AMR) AF: 0.00 AC: 0 AN: 32790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18142

East Asian (EAS) AF: 0.00 AC: 0 AN: 33748

South Asian (SAS) AF: 0.00 AC: 0 AN: 59718

European-Finnish (FIN) AF: 0.000104 AC: 4 AN: 38284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2530

European-Non Finnish (NFE) AF: 0.00000487 AC: 2 AN: 410470

Other (OTH) AF: 0.00 AC: 0 AN: 32844

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2236534; hg19: chr10-44874309;