rs12075

Positions:

chr1-159205564-G-A

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ACKR1	NM_002036.4 linkuse as main transcript	c.125G>A	p.Gly42Asp	missense_variant	2/2	ENST00000368122.4	NP_002027.2
ACKR1	NM_001122951.3 linkuse as main transcript	c.131G>A	p.Gly44Asp	missense_variant	2/2		NP_001116423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACKR1	ENST00000368122.4 linkuse as main transcript	c.125G>A	p.Gly42Asp	missense_variant	2/2	1	NM_002036.4	ENSP00000357104	P2	Q16570-1
ACKR1	ENST00000368121.6 linkuse as main transcript	c.131G>A	p.Gly44Asp	missense_variant	2/2			ENSP00000357103	A2	Q16570-2
ACKR1	ENST00000435307.2 linkuse as main transcript	n.306G>A		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1 linkuse as main transcript	n.164+2246C>T		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes

AF:

0.512

AC:

128658

AN:

251268

Hom.:

37310

AF XY:

0.506

AC XY:

68752

AN XY:

135808

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 SAS exome

AF:

0.383

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

Gnomad4 AFR exome

AF:

0.939

Gnomad4 AMR exome

AF:

0.448

Gnomad4 ASJ exome

AF:

0.553

Gnomad4 EAS exome

AF:

0.0785

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.579

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.642

AC:

97720

AN:

152204

Hom.:

34587

Cov.:

AF XY:

0.629

AC XY:

46835

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.923

Gnomad4 AMR

AF:

0.566

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.0634

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.499

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.579

Hom.:

65875

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 27, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

ACKR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

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

Benign, no assertion criteria provided

literature only

OMIM

Aug 10, 2015

- -

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

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;.;.

MutationTaster

Benign

1.0

P;P;P;P

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

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over