rs1045879

Variant names:

• chr2-236581261-C-T
• rs1045879
• NM_020311.3:c.796C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020311.3(ACKR3):​c.796C>T​(p.Leu266Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,613,720 control chromosomes in the GnomAD database, including 70,825 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 0.36 (12731 hom., cov: 33)
  • Exomes 𝑓: 0.27 (58094 hom.)
• Consequence: ACKR3 NM_020311.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.859
• Publications: 20 publications found

Genes affected

ACKR3 (HGNC:23692): (atypical chemokine receptor 3) This gene encodes a member of the G-protein coupled receptor family. Although this protein was earlier thought to be a receptor for vasoactive intestinal peptide (VIP), it is now considered to be an orphan receptor, in that its endogenous ligand has not been identified. The protein is also a coreceptor for human immunodeficiency viruses (HIV). Translocations involving this gene and HMGA2 on chromosome 12 have been observed in lipomas. [provided by RefSeq, Jul 2008]

ACKR3 Gene-Disease associations (from GenCC):

• oculomotor-abducens synkinesis

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.859 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020311.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR3	NM_020311.3	MANE Select	c.796C>T	p.Leu266Leu	synonymous	Exon 2 of 2	NP_064707.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR3	ENST00000272928.4	TSL:2 MANE Select	c.796C>T	p.Leu266Leu	synonymous	Exon 2 of 2	ENSP00000272928.3
	ACKR3	ENST00000929731.1		c.796C>T	p.Leu266Leu	synonymous	Exon 2 of 2	ENSP00000599790.1
	ACKR3	ENST00000946093.1		c.796C>T	p.Leu266Leu	synonymous	Exon 3 of 3	ENSP00000616152.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54152 AN: 151986 Hom.: 12693 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.255 AC: 64055 AN: 251410 AF XY: 0.257

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.0322

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.268 AC: 391137 AN: 1461616 Hom.: 58094 Cov.: 35 AF XY: 0.269 AC XY: 195894 AN XY: 727088

African (AFR) AF: 0.679 AC: 22741 AN: 33470

American (AMR) AF: 0.167 AC: 7453 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 6364 AN: 26132

East Asian (EAS) AF: 0.0163 AC: 649 AN: 39698

South Asian (SAS) AF: 0.330 AC: 28443 AN: 86252

European-Finnish (FIN) AF: 0.171 AC: 9137 AN: 53342

Middle Eastern (MID) AF: 0.349 AC: 2013 AN: 5768

European-Non Finnish (NFE) AF: 0.267 AC: 297170 AN: 1111842

Other (OTH) AF: 0.284 AC: 17167 AN: 60388

GnomAD4 genome AF: 0.357 AC: 54234 AN: 152104 Hom.: 12731 Cov.: 33 AF XY: 0.346 AC XY: 25741 AN XY: 74376

African (AFR) AF: 0.668 AC: 27685 AN: 41450

American (AMR) AF: 0.231 AC: 3527 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3472

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5174

South Asian (SAS) AF: 0.317 AC: 1525 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1720 AN: 10596

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17862 AN: 67978

Other (OTH) AF: 0.321 AC: 678 AN: 2112

Alfa AF: 0.283 Hom.: 21651

Bravo AF: 0.371

Asia WGS AF: 0.181 AC: 631 AN: 3478

EpiCase AF: 0.271

EpiControl AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.4
DANN	Benign	0.71
PhyloP100		0.86
Mutation Taster		=98/2	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: rs1045879; hg19: chr2-237489904; COSMIC: COSV56021444; COSMIC: COSV56021444;