Variant 1-159205753-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002036.4(ACKR1):c.314G>A(p.Gly105Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ACKR1
NM_002036.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACKR1	NM_002036.4 linkuse as main transcript	c.314G>A	p.Gly105Asp	missense_variant	2/2	ENST00000368122.4	NP_002027.2	Q16570-1Q5Y7A2
ACKR1	NM_001122951.3 linkuse as main transcript	c.320G>A	p.Gly107Asp	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.314G>A	p.Gly105Asp	missense_variant	2/2	1	NM_002036.4	ENSP00000357104.1	Q16570-1
ACKR1	ENST00000368121.6 linkuse as main transcript	c.320G>A	p.Gly107Asp	missense_variant	2/2	6		ENSP00000357103.2	Q16570-2
ACKR1	ENST00000435307.2 linkuse as main transcript	n.495G>A		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1 linkuse as main transcript	n.164+2057C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000722

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

251022

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.320G>A (p.G107D) alteration is located in exon 1 (coding exon 1) of the ACKR1 gene. This alteration results from a G to A substitution at nucleotide position 320, causing the glycine (G) at amino acid position 107 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T;.;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Benign

0.75

LIST_S2

Pathogenic

0.98

D;.;.;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.53

D;D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.8

L;L;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.85

MVP

0.48

MPC

0.23

ClinPred

0.69

GERP RS

5.1

Varity_R

0.67

gMVP

0.83

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.

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