3-42818461-C-T

Position:

• chr3-42818461-C-T

Variant summary

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

The NM_001296.5(ACKR2):​c.-118-1170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,062 control chromosomes in the GnomAD database, including 30,293 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 0.62 (30293 hom., cov: 32)
• Consequence: ACKR2 NM_001296.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

ACKR2 (HGNC:1565): (atypical chemokine receptor 2) This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this receptor in lymphatic endothelial cells and overexpression in vascular tumors suggested its function in chemokine-driven recirculation of leukocytes and possible chemokine effects on the development and growth of vascular tumors. This receptor appears to bind the majority of beta-chemokine family members; however, its specific function remains unknown. This gene is mapped to chromosome 3p21.3, a region that includes a cluster of chemokine receptor genes. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACKR2	NM_001296.5	c.-118-1170C>T		intron_variant		ENST00000422265.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACKR2	ENST00000422265.6	c.-118-1170C>T		intron_variant		1	NM_001296.5	P1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93587 AN: 151944 Hom.: 30278 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.616 AC: 93645 AN: 152062 Hom.: 30293 Cov.: 32 AF XY: 0.619 AC XY: 46024 AN XY: 74330

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.649

Alfa AF: 0.658 Hom.: 6804

Bravo AF: 0.615

Asia WGS AF: 0.706 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4683336; hg19: chr3-42859953;