2-236542392-C-G

Variant names:

• chr2-236542392-C-G
• rs6431472
• ENST00000780274.1:n.250+2239C>G

Variant summary

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

The ENST00000780274.1(ENSG00000301621):​n.250+2239C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,092 control chromosomes in the GnomAD database, including 6,095 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 0.23 (6095 hom., cov: 32)
• Consequence: ENSG00000301621 ENST00000780274.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 5 publications found

Genes affected

ENSG00000301621 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACKR3	XM_005246098.4	c.-136+5045C>G		intron_variant	Intron 1 of 2		XP_005246155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000301621	ENST00000780274.1	n.250+2239C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35668 AN: 151974 Hom.: 6074 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.235 AC: 35727 AN: 152092 Hom.: 6095 Cov.: 32 AF XY: 0.229 AC XY: 16995 AN XY: 74342

African (AFR) AF: 0.488 AC: 20217 AN: 41460

American (AMR) AF: 0.145 AC: 2216 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 453 AN: 3466

East Asian (EAS) AF: 0.168 AC: 870 AN: 5168

South Asian (SAS) AF: 0.162 AC: 780 AN: 4816

European-Finnish (FIN) AF: 0.0980 AC: 1038 AN: 10594

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9679 AN: 67984

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.0870 Hom.: 115

Bravo AF: 0.250

Asia WGS AF: 0.182 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.34
PhyloP100		0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6431472; hg19: chr2-237451035;