2-236545163-G-T

Variant names:

• chr2-236545163-G-T
• rs4571012
• XM_005246098.4:c.-136+7816G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000780274.1(ENSG00000301621):​n.251-294G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,060 control chromosomes in the GnomAD database, including 9,425 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 0.28 (9425 hom., cov: 32)
• Consequence: ENSG00000301621 ENST00000780274.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 7 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)

ENSG00000301621 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000780274.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000301621	ENST00000780274.1		n.251-294G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41943 AN: 151942 Hom.: 9386 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.276 AC: 42027 AN: 152060 Hom.: 9425 Cov.: 32 AF XY: 0.269 AC XY: 19992 AN XY: 74326

African (AFR) AF: 0.628 AC: 26022 AN: 41440

American (AMR) AF: 0.162 AC: 2474 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.168 AC: 865 AN: 5154

South Asian (SAS) AF: 0.162 AC: 781 AN: 4814

European-Finnish (FIN) AF: 0.106 AC: 1123 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9765 AN: 67974

Other (OTH) AF: 0.226 AC: 477 AN: 2108

Alfa AF: 0.140 Hom.: 1023

Bravo AF: 0.296

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.43
PhyloP100		-0.11

Splicing

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

dbSNP: rs4571012;

hg19: chr2-237453806;