10-44375898-G-A

Variant names:

• chr10-44375898-G-A
• rs17881575
• ENST00000374426:c.*41C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001033886.2(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 NM_001033886.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -18 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CXCL12	NM_001033886.2	c.*41C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001029058.1
CXCL12	NM_001277990.2	c.110-2808C>T		intron_variant	Intron 2 of 2		NP_001264919.1
CXCL12	NM_000609.7	c.267-2555C>T		intron_variant	Intron 3 of 3		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374426	c.*41C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363548.2
CXCL12	ENST00000374429.6	c.267-2555C>T		intron_variant	Intron 3 of 3	1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-2808C>T		intron_variant	Intron 2 of 2	5		ENSP00000379139.3

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

GnomAD2 exomes AF: 0.0832 AC: 20634 AN: 247902 AF XY: 0.0837

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 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 AC: 487 AN: 32836

Gnomad4 AMR exome AF: 0.0872 AC: 3807 AN: 43664

Gnomad4 ASJ exome AF: 0.0675 AC: 1755 AN: 25988

Gnomad4 EAS exome AF: 0.101 AC: 4015 AN: 39678

Gnomad4 SAS exome AF: 0.0680 AC: 5796 AN: 85184

Gnomad4 FIN exome AF: 0.0766 AC: 4088 AN: 53362

Gnomad4 NFE exome AF: 0.0987 AC: 109643 AN: 1110898

Gnomad4 Remaining exome AF: 0.0866 AC: 5190 AN: 59960

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 AC: 0.0195371 AN: 0.0195371

Gnomad4 AMR AF: 0.0819 AC: 0.0819287 AN: 0.0819287

Gnomad4 ASJ AF: 0.0681 AC: 0.06809 AN: 0.06809

Gnomad4 EAS AF: 0.0941 AC: 0.0941496 AN: 0.0941496

Gnomad4 SAS AF: 0.0664 AC: 0.0664176 AN: 0.0664176

Gnomad4 FIN AF: 0.0774 AC: 0.0773798 AN: 0.0773798

Gnomad4 NFE AF: 0.0957 AC: 0.0957303 AN: 0.0957303

Gnomad4 OTH AF: 0.0909 AC: 0.0909091 AN: 0.0909091

Alfa AF: 0.0906 Hom.: 870

Bravo AF: 0.0698

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.85
Mutation Taster		=100/0	polymorphism (auto)

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;