rs1804429

Positions:

• chr10-44370393-A-C
• chr10-44370393-A-G
• chr10-44370393-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277990.2(CXCL12):​c.*2495T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,736 control chromosomes in the GnomAD database, including 185 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 0.046 (185 hom., cov: 33)
  • Exomes 𝑓: 0.0099 (0 hom.)
• Consequence: CXCL12 NM_001277990.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.*2495T>G		3_prime_UTR_variant	3/3		NP_001264919.1
CXCL12	NM_000609.7	c.*2935T>G		3_prime_UTR_variant	4/4		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.*2935T>G		3_prime_UTR_variant	4/4	1		ENSP00000363551.2

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6929 AN: 152212 Hom.: 185 Cov.: 33

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.0611

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.00985 AC: 4 AN: 406 Hom.: 0 Cov.: 0 AF XY: 0.0164 AC XY: 4 AN XY: 244

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0456 AC: 6946 AN: 152330 Hom.: 185 Cov.: 33 AF XY: 0.0446 AC XY: 3322 AN XY: 74486

Gnomad4 AFR AF: 0.0748

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.0618

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0333 Hom.: 108

Bravo AF: 0.0476

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1804429; hg19: chr10-44865841;