NM_001296.5:c.-118-1170C>T

Variant names:

• chr3-42818461-C-T
• rs4683336
• NM_001296.5:c.-118-1170C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ENSG00000290317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001296.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR2	NM_001296.5	MANE Select	c.-118-1170C>T		intron	N/A	NP_001287.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR2	ENST00000422265.6	TSL:1 MANE Select	c.-118-1170C>T		intron	N/A	ENSP00000416996.1
	ACKR2	ENST00000442925.5	TSL:1	c.-38+8929C>T		intron	N/A	ENSP00000396150.1
	ENSG00000290317	ENST00000426937.5	TSL:3	c.-244-1170C>T		intron	N/A	ENSP00000413859.1

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

African (AFR) AF: 0.406 AC: 16821 AN: 41462

American (AMR) AF: 0.730 AC: 11160 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4161 AN: 5158

South Asian (SAS) AF: 0.679 AC: 3272 AN: 4816

European-Finnish (FIN) AF: 0.670 AC: 7077 AN: 10564

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46567 AN: 67976

Other (OTH) AF: 0.649 AC: 1371 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.16
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4683336; hg19: chr3-42859953;