2-236581263-G-A

Variant names:

• chr2-236581263-G-A
• NM_020311.3:c.798G>A
• ACKR3 p.Leu266Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020311.3(ACKR3):​c.798G>A​(p.Leu266Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ACKR3 NM_020311.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.368 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR3	NM_020311.3	MANE Select	c.798G>A	p.Leu266Leu	synonymous	Exon 2 of 2	NP_064707.1	P25106

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR3	ENST00000272928.4	TSL:2 MANE Select	c.798G>A	p.Leu266Leu	synonymous	Exon 2 of 2	ENSP00000272928.3	P25106
	ACKR3	ENST00000929731.1		c.798G>A	p.Leu266Leu	synonymous	Exon 2 of 2	ENSP00000599790.1
	ACKR3	ENST00000946093.1		c.798G>A	p.Leu266Leu	synonymous	Exon 3 of 3	ENSP00000616152.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-237489906;