rs1045879

chr2-236581261-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020311.3(ACKR3):c.796C>T(p.Leu266=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACKR3	NM_020311.3	c.796C>T	p.Leu266=	synonymous_variant	2/2	ENST00000272928.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACKR3	ENST00000272928.4	c.796C>T	p.Leu266=	synonymous_variant	2/2	2	NM_020311.3	P1

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

GnomAD3 exomes AF: 0.255 AC: 64055 AN: 251410 Hom.: 10518 AF XY: 0.257 AC XY: 34962 AN XY: 135882

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 SAS exome AF: 0.325

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

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.0163

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.284

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

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.321

Alfa AF: 0.276 Hom.: 14862

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	5.4
Dann	Benign	0.71

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: rs1045879; hg19: chr2-237489904; COSMIC: COSV56021444; COSMIC: COSV56021444;