ENST00000374429.6:c.*2568G>C

Variant names:

• chr10-44370760-C-G
• rs266093
• ENST00000374429.6:c.*2568G>C

Variant summary

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

The ENST00000374429.6(CXCL12):​c.*2568G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,156 control chromosomes in the GnomAD database, including 28,009 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 0.60 (28005 hom., cov: 33)
  • Exomes 𝑓: 0.46 (4 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 22 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374429.6. 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.*2128G>C		3_prime_UTR	Exon 3 of 3	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.*2568G>C		3_prime_UTR	Exon 4 of 4	NP_000600.1	P48061-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.*2568G>C		3_prime_UTR	Exon 4 of 4	ENSP00000363551.2	P48061-1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90742 AN: 151992 Hom.: 27980 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.648

GnomAD4 exome AF: 0.457 AC: 21 AN: 46 Hom.: 4 Cov.: 0 AF XY: 0.533 AC XY: 16 AN XY: 30

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.368 AC: 14 AN: 38

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.597 AC: 90809 AN: 152110 Hom.: 28005 Cov.: 33 AF XY: 0.607 AC XY: 45145 AN XY: 74364

African (AFR) AF: 0.433 AC: 17961 AN: 41476

American (AMR) AF: 0.731 AC: 11173 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2262 AN: 3470

East Asian (EAS) AF: 0.816 AC: 4216 AN: 5164

South Asian (SAS) AF: 0.738 AC: 3563 AN: 4826

European-Finnish (FIN) AF: 0.698 AC: 7393 AN: 10590

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42093 AN: 67974

Other (OTH) AF: 0.653 AC: 1380 AN: 2114

Alfa AF: 0.472 Hom.: 1307

Bravo AF: 0.593

Asia WGS AF: 0.733 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.62
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs266093; hg19: chr10-44866208;