10-44375898-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000374426.6(CXCL12):c.*41C>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 0.0906 in 1,607,966 control chromosomes in the GnomAD database, including 7,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (470 hom., cov: 33)
  • Exomes 𝑓: 0.093 (6596 hom.)
• Consequence: CXCL12 ENST00000374426.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.340

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=-0.45).
• BP6: Variant 10-44375898-G-A is Benign according to our data. Variant chr10-44375898-G-A is described in ClinVar as [Benign]. Clinvar id is 1220639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_001033886.2	c.*41C>T		3_prime_UTR_variant	4/4
CXCL12	NM_000609.7	c.267-2555C>T		intron_variant
CXCL12	NM_001277990.2	c.110-2808C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000374426.6	c.*41C>T		3_prime_UTR_variant	4/4	1
CXCL12	ENST00000374429.6	c.267-2555C>T		intron_variant		1		A1
CXCL12	ENST00000395793.7	c.110-2808C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10697 AN: 152138 Hom.: 471 Cov.: 33

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.0939

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0919

GnomAD3 exomes AF: 0.0832 AC: 20634 AN: 247902 Hom.: 959 AF XY: 0.0837 AC XY: 11210 AN XY: 133998

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.0858

Gnomad ASJ exome AF: 0.0683

Gnomad EAS exome AF: 0.0945

Gnomad SAS exome AF: 0.0660

Gnomad FIN exome AF: 0.0783

Gnomad NFE exome AF: 0.0966

Gnomad OTH exome AF: 0.0920

GnomAD4 exome AF: 0.0928 AC: 135069 AN: 1455710 Hom.: 6596 Cov.: 31 AF XY: 0.0920 AC XY: 66609 AN XY: 724134

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.0872

Gnomad4 ASJ exome AF: 0.0675

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0680

Gnomad4 FIN exome AF: 0.0766

Gnomad4 NFE exome AF: 0.0987

Gnomad4 OTH exome AF: 0.0866

GnomAD4 genome AF: 0.0702 AC: 10690 AN: 152256 Hom.: 470 Cov.: 33 AF XY: 0.0699 AC XY: 5200 AN XY: 74434

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0681

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.0664

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.0909

Alfa AF: 0.0943 Hom.: 699

Bravo AF: 0.0698

Asia WGS AF: 0.0620 AC: 216 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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	18
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17881575; hg19: chr10-44871346; COSMIC: COSV59108875; COSMIC: COSV59108875;