Variant 1-159205638-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002036.4(ACKR1):c.199C>T(p.Leu67Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,614,208 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.0060 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 194 hom. )

Consequence

ACKR1
NM_002036.4 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: -0.236

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:

ACKR1 (HGNC:):

ACKR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016512573).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0838 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.199C>T	p.Leu67Phe	missense_variant	2/2	ENST00000368122.4	NP_002027.2	Q16570-1Q5Y7A2
ACKR1	NM_001122951.3 linkuse as main transcript	c.205C>T	p.Leu69Phe	missense_variant	2/2		NP_001116423.1	Q16570-2Q5Y7A1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACKR1	ENST00000368122.4 linkuse as main transcript	c.199C>T	p.Leu67Phe	missense_variant	2/2	1	NM_002036.4	ENSP00000357104.1	Q16570-1
ACKR1	ENST00000368121.6 linkuse as main transcript	c.205C>T	p.Leu69Phe	missense_variant	2/2	6		ENSP00000357103.2	Q16570-2
ACKR1	ENST00000435307.2 linkuse as main transcript	n.380C>T		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1 linkuse as main transcript	n.164+2172G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

915

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0906

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.0120

AC:

3017

AN:

251108

Hom.:

124

AF XY:

0.0109

AC XY:

1475

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.00353

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.000511

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.00358

AC:

5238

AN:

1461858

Hom.:

194

Cov.:

AF XY:

0.00341

AC XY:

2483

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.0691

Gnomad4 SAS exome

AF:

0.00350

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.000213

Gnomad4 OTH exome

AF:

0.00972

GnomAD4 genome

AF:

0.00600

AC:

914

AN:

152350

Hom.:

Cov.:

AF XY:

0.00718

AC XY:

535

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0906

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00340

Hom.:

Bravo

AF:

0.00589

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0105

AC:

1279

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Duffy Blood group system

Other:1

Affects, no assertion criteria provided

research

Australian Red Cross Blood Service

Jul 01, 2021

reduced expression of Fy(a) antigen observed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.81

T;.;.;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;.;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Benign

0.073

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.058

MPC

0.032

ClinPred

0.067

GERP RS

-4.1

Varity_R

0.12

gMVP

0.48

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

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