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GeneBe

2-236581095-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020311.3(ACKR3):c.630C>T(p.Ile210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000397 in 1,614,224 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 3 hom. )

Consequence

ACKR3
NM_020311.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.657
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-236581095-C-T is Benign according to our data. Variant chr2-236581095-C-T is described in ClinVar as [Benign]. Clinvar id is 710902.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.657 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACKR3NM_020311.3 linkuse as main transcriptc.630C>T p.Ile210= synonymous_variant 2/2 ENST00000272928.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACKR3ENST00000272928.4 linkuse as main transcriptc.630C>T p.Ile210= synonymous_variant 2/22 NM_020311.3 P1
ACKR3ENST00000447924.1 linkuse as main transcriptc.630C>T p.Ile210= synonymous_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00211
AC:
321
AN:
152218
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00716
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000665
AC:
167
AN:
251196
Hom.:
1
AF XY:
0.000479
AC XY:
65
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00874
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000219
AC:
320
AN:
1461888
Hom.:
3
Cov.:
31
AF XY:
0.000171
AC XY:
124
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00714
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.000464
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00211
AC:
321
AN:
152336
Hom.:
2
Cov.:
33
AF XY:
0.00200
AC XY:
149
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00714
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000900
Hom.:
0
Bravo
AF:
0.00250
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
11
Dann
Benign
0.84

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146961395; hg19: chr2-237489738; COSMIC: COSV56021663; API