Genetic Variant ACKR1:p.Ala100Thr (chr1-159205737-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002036.4(ACKR1):c.298G>A(p.Ala100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,614,076 control chromosomes in the GnomAD database, including 20,888 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1346 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19542 hom. )

Consequence

ACKR1
NM_002036.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.580

Publications

53 publications found

Variant links:

Genes affected

ACKR1 (HGNC:4035): (atypical chemokine receptor 1 (Duffy blood group)) The protein encoded by this gene is a glycosylated membrane protein and a non-specific receptor for several chemokines. The encoded protein is the receptor for the human malarial parasites Plasmodium vivax and Plasmodium knowlesi. Polymorphisms in this gene are the basis of the Duffy blood group system. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACKR1 links:

CADM3-AS1 (HGNC:40812): (CADM3 antisense RNA 1)

CADM3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016954243).

BP6

Variant 1-159205737-G-A is Benign according to our data. Variant chr1-159205737-G-A is described in ClinVar as [Benign]. Clinvar id is 3056036.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACKR1	NM_002036.4 link	c.298G>A	p.Ala100Thr	missense_variant	Exon 2 of 2	ENST00000368122.4	NP_002027.2	Q16570-1Q5Y7A2
ACKR1	NM_001122951.3 link	c.304G>A	p.Ala102Thr	missense_variant	Exon 2 of 2		NP_001116423.1	Q16570-2Q5Y7A1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACKR1	ENST00000368122.4 link	c.298G>A	p.Ala100Thr	missense_variant	Exon 2 of 2	1	NM_002036.4	ENSP00000357104.1		Q16570-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17293

AN:

152120

Hom.:

1346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0922

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.116

GnomAD2 exomes

AF:

0.124

AC:

30982

AN:

250858

AF XY:

0.129

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.0650

Gnomad ASJ exome

AF:

0.0645

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.156

AC:

228594

AN:

1461838

Hom.:

19542

Cov.:

AF XY:

0.156

AC XY:

113218

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0228

AC:

763

AN:

33480

American (AMR)

AF:

0.0683

AC:

3055

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

1566

AN:

26136

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.121

AC:

10442

AN:

86258

European-Finnish (FIN)

AF:

0.179

AC:

9560

AN:

53366

Middle Eastern (MID)

AF:

0.0711

AC:

410

AN:

5768

European-Non Finnish (NFE)

AF:

0.175

AC:

194664

AN:

1112010

Other (OTH)

AF:

0.135

AC:

8124

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13415

26830

40245

53660

67075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.114

AC:

17285

AN:

152238

Hom.:

1346

Cov.:

AF XY:

0.111

AC XY:

8296

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0291

AC:

1209

AN:

41538

American (AMR)

AF:

0.0920

AC:

1408

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

208

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5182

South Asian (SAS)

AF:

0.108

AC:

521

AN:

4818

European-Finnish (FIN)

AF:

0.176

AC:

1869

AN:

10604

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11705

AN:

67996

Other (OTH)

AF:

0.114

AC:

242

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

773

1546

2318

3091

3864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.151

Hom.:

3547

Bravo

AF:

0.102

TwinsUK

AF:

0.171

AC:

635

ALSPAC

AF:

0.167

AC:

644

ESP6500AA

AF:

0.0318

AC:

140

ESP6500EA

AF:

0.171

AC:

1467

ExAC

AF:

0.127

AC:

15371

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.163

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ACKR1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.71

T;.;.;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;.;.

PhyloP100

0.58

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

N;N;D;N

REVEL

Benign

0.13

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.97

D;D;.;.

Vest4

0.042

MPC

0.030

ClinPred

0.010

GERP RS

3.1

Varity_R

0.066

gMVP

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-159205737-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over