rs3780891

Positions:

• chr10-44383265-G-A
• chr10-44383265-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199168.4(CXCL12):​c.61+1680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,238 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.075 (487 hom., cov: 32)
• Consequence: CXCL12 NM_199168.4 intron
• Scores: Splicing: ADA: 0.00005694
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL12	NM_199168.4	c.61+1680C>T		intron_variant		ENST00000343575.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL12	ENST00000343575.11	c.61+1680C>T		intron_variant		1	NM_199168.4	P4

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11482 AN: 152120 Hom.: 488 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.0975

GnomAD3 exomes AF: 0.114 AC: 5 AN: 44 Hom.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.167

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

GnomAD4 genome AF: 0.0754 AC: 11480 AN: 152238 Hom.: 487 Cov.: 32 AF XY: 0.0750 AC XY: 5580 AN XY: 74448

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.0951

Gnomad4 SAS AF: 0.0670

Gnomad4 FIN AF: 0.0782

Gnomad4 NFE AF: 0.0967

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.0723 Hom.: 224

Bravo AF: 0.0750

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3780891; hg19: chr10-44878713;