10-44373578-C-T

Variant names:

• chr10-44373578-C-T
• rs3780890
• ENST00000374429.6:c.267-235G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277990.2(CXCL12):​c.110-488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,202 control chromosomes in the GnomAD database, including 3,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3240 hom., cov: 33)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.785

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-44373578-C-T is Benign according to our data. Variant chr10-44373578-C-T is described in ClinVar as [Benign]. Clinvar id is 1272932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.110-488G>A		intron_variant	Intron 2 of 2		NP_001264919.1
CXCL12	NM_000609.7	c.267-235G>A		intron_variant	Intron 3 of 3		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-235G>A		intron_variant	Intron 3 of 3	1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-488G>A		intron_variant	Intron 2 of 2	5		ENSP00000379139.3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29319 AN: 152082 Hom.: 3229 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29344 AN: 152202 Hom.: 3240 Cov.: 33 AF XY: 0.195 AC XY: 14538 AN XY: 74412

Gnomad4 AFR AF: 0.109 AC: 0.109367 AN: 0.109367

Gnomad4 AMR AF: 0.199 AC: 0.199033 AN: 0.199033

Gnomad4 ASJ AF: 0.249 AC: 0.249424 AN: 0.249424

Gnomad4 EAS AF: 0.438 AC: 0.438396 AN: 0.438396

Gnomad4 SAS AF: 0.274 AC: 0.274461 AN: 0.274461

Gnomad4 FIN AF: 0.203 AC: 0.203172 AN: 0.203172

Gnomad4 NFE AF: 0.211 AC: 0.21135 AN: 0.21135

Gnomad4 OTH AF: 0.228 AC: 0.228261 AN: 0.228261

Alfa AF: 0.123 Hom.: 264

Bravo AF: 0.187

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.72
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: rs3780890; hg19: chr10-44869026;