rs1801157

chr10-44372809-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000374429.6(CXCL12):c.*519G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,472,396 control chromosomes in the GnomAD database, including 28,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2405 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25890 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-44372809-C-T is Benign according to our data. Variant chr10-44372809-C-T is described in ClinVar as [Benign]. Clinvar id is 1291069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_000609.7	c.*519G>A		3_prime_UTR_variant	4/4
CXCL12	NM_001277990.2	c.*79G>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000374429.6	c.*519G>A		3_prime_UTR_variant	4/4	1		A1
CXCL12	ENST00000395793.7	c.*79G>A		3_prime_UTR_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24815 AN: 152020 Hom.: 2395 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.195 AC: 257184 AN: 1320258 Hom.: 25890 Cov.: 35 AF XY: 0.196 AC XY: 126557 AN XY: 644322

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.163 AC: 24838 AN: 152138 Hom.: 2405 Cov.: 32 AF XY: 0.165 AC XY: 12275 AN XY: 74378

Gnomad4 AFR AF: 0.0621

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.191

Alfa AF: 0.184 Hom.: 1411

Bravo AF: 0.157

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

This variant is associated with the following publications: (PMID: 23325742, 19601773, 16306115, 22962615, 24361877, 23615182, 18928397, 9430590, 27832196) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.013
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801157; hg19: chr10-44868257; COSMIC: COSV59107693; COSMIC: COSV59107693;