chr1-159205564-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002036.4(ACKR1):c.125G>A(p.Gly42Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,613,990 control chromosomes in the GnomAD database, including 269,798 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 34587 hom., cov: 33)

Exomes 𝑓: 0.56 ( 235211 hom. )

Consequence

ACKR1
NM_002036.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.192

Publications

190 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.9943995E-7).

BP6

Variant 1-159205564-G-A is Benign according to our data. Variant chr1-159205564-G-A is described in ClinVar as Benign. ClinVar VariationId is 17728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACKR1	NM_002036.4 link	c.125G>A	p.Gly42Asp	missense_variant	Exon 2 of 2	ENST00000368122.4	NP_002027.2	Q16570-1Q5Y7A2
ACKR1	NM_001122951.3 link	c.131G>A	p.Gly44Asp	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.125G>A	p.Gly42Asp	missense_variant	Exon 2 of 2	1	NM_002036.4	ENSP00000357104.1		Q16570-1

Frequencies

GnomAD3 genomes

AF:

0.642

AC:

97626

AN:

152086

Hom.:

34532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.923

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.0638

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.659

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.634

GnomAD2 exomes

AF:

0.512

AC:

128658

AN:

251268

AF XY:

0.506

show subpopulations

Gnomad AFR exome

AF:

0.933

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.552

Gnomad EAS exome

AF:

0.0498

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.579

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.555

AC:

811380

AN:

1461786

Hom.:

235211

Cov.:

AF XY:

0.548

AC XY:

398869

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.939

AC:

31446

AN:

33480

American (AMR)

AF:

0.448

AC:

20045

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

14459

AN:

26130

East Asian (EAS)

AF:

0.0785

AC:

3117

AN:

39700

South Asian (SAS)

AF:

0.384

AC:

33116

AN:

86250

European-Finnish (FIN)

AF:

0.518

AC:

27695

AN:

53414

Middle Eastern (MID)

AF:

0.655

AC:

3780

AN:

5768

European-Non Finnish (NFE)

AF:

0.579

AC:

643729

AN:

1111938

Other (OTH)

AF:

0.563

AC:

33993

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

21481

42962

64443

85924

107405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17526

35052

52578

70104

87630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.642

AC:

97720

AN:

152204

Hom.:

34587

Cov.:

AF XY:

0.629

AC XY:

46835

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.923

AC:

38367

AN:

41554

American (AMR)

AF:

0.566

AC:

8666

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1949

AN:

3472

East Asian (EAS)

AF:

0.0634

AC:

328

AN:

5174

South Asian (SAS)

AF:

0.376

AC:

1814

AN:

4822

European-Finnish (FIN)

AF:

0.499

AC:

5285

AN:

10582

Middle Eastern (MID)

AF:

0.664

AC:

194

AN:

292

European-Non Finnish (NFE)

AF:

0.579

AC:

39348

AN:

67976

Other (OTH)

AF:

0.628

AC:

1327

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1515

3030

4546

6061

7576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.596

Hom.:

106376

Bravo

AF:

0.657

TwinsUK

AF:

0.576

AC:

2137

ALSPAC

AF:

0.571

AC:

2199

ESP6500AA

AF:

0.916

AC:

4037

ESP6500EA

AF:

0.578

AC:

4967

ExAC

AF:

0.523

AC:

63517

Asia WGS

AF:

0.275

AC:

962

AN:

3478

EpiCase

AF:

0.580

EpiControl

AF:

0.591

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 27, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Gly42Asp in exon 2 of DARC: This variant is not expected to have clinical sign ificance because it has been identified in 92.68% (9644/10406) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs12075). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

ACKR1-related disorder

Benign:1

Oct 16, 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). -

DUFFY BLOOD GROUP SYSTEM, FYA/FYB POLYMORPHISM

Benign:1

Aug 10, 2015

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.68

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.060

T;T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.45

T;.;.;T

MetaRNN

Benign

9.0e-7

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

N;N;.;.

PhyloP100

0.19

PrimateAI

Benign

0.33

PROVEAN

Benign

1.5

N;N;N;N

REVEL

Benign

0.036

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.91

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.019

MPC

0.030

ClinPred

0.0062

GERP RS

-1.1

Varity_R

0.035

gMVP

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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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