10-44378544-C-CCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_199168.4(CXCL12):c.*88_*89insAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,596,194 control chromosomes in the GnomAD database, including 56,097 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4623 hom., cov: 26)
  • Exomes 𝑓: 0.26 (51474 hom.)
• Consequence: CXCL12 NM_199168.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46

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 -10 ACMG points.

• BP6: Variant 10-44378544-C-CCT is Benign according to our data. Variant chr10-44378544-C-CCT is described in ClinVar as [Benign]. Clinvar id is 1274726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_199168.4	c.*88_*89insAG		3_prime_UTR_variant	3/3	ENST00000343575.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000343575.11	c.*88_*89insAG		3_prime_UTR_variant	3/3	1	NM_199168.4	P4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34039 AN: 151916 Hom.: 4622 Cov.: 26

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.260 AC: 375834 AN: 1444160 Hom.: 51474 Cov.: 34 AF XY: 0.258 AC XY: 185276 AN XY: 716924

Gnomad4 AFR exome AF: 0.0747

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.224 AC: 34042 AN: 152034 Hom.: 4623 Cov.: 26 AF XY: 0.231 AC XY: 17138 AN XY: 74294

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.250

Alfa AF: 0.241 Hom.: 605

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 10, 2018

This variant is associated with the following publications: (PMID: 30266500) -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2839694; hg19: chr10-44873992;