ENST00000374429.6:c.*519G>T

Variant names:

• chr10-44372809-C-A
• rs1801157
• ENST00000374429.6:c.*519G>T

Variant summary

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

The ENST00000374429.6(CXCL12):​c.*519G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,320,386 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: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• 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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.*79G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001264919.1
CXCL12	NM_000609.7	c.*519G>T		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.*519G>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.*79G>T		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000379139.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1320386 Hom.: 0 Cov.: 35 AF XY: 0.00000155 AC XY: 1 AN XY: 644394

African (AFR) AF: 0.00 AC: 0 AN: 29620

American (AMR) AF: 0.0000731 AC: 2 AN: 27358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20864

East Asian (EAS) AF: 0.00 AC: 0 AN: 35204

South Asian (SAS) AF: 0.00 AC: 0 AN: 68214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3848

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048808

Other (OTH) AF: 0.00 AC: 0 AN: 54946

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0070
DANN	Benign	0.39
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs1801157; hg19: chr10-44868257;