Variant chr1-159205704-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_002036.4(ACKR1):c.265C>A(p.Arg89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R89C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACKR1
NM_002036.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.887

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:

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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;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-159205704-C-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.13313958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACKR1	NM_002036.4 linkuse as main transcript	c.265C>A	p.Arg89Ser	missense_variant	2/2	ENST00000368122.4	NP_002027.2
ACKR1	NM_001122951.3 linkuse as main transcript	c.271C>A	p.Arg91Ser	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.265C>A	p.Arg89Ser	missense_variant	2/2	1	NM_002036.4	ENSP00000357104	P2	Q16570-1
ACKR1	ENST00000368121.6 linkuse as main transcript	c.271C>A	p.Arg91Ser	missense_variant	2/2			ENSP00000357103	A2	Q16570-2
ACKR1	ENST00000435307.2 linkuse as main transcript	n.446C>A		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1 linkuse as main transcript	n.164+2106G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

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:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.096

T;T;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.93

D;.;.;D

M_CAP

Benign

0.0097

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.89

N;N;N;N

REVEL

Benign

0.065

Sift

Benign

0.11

T;T;D;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.30

B;B;.;.

Vest4

0.12

MutPred

0.36

Loss of catalytic residue at R89 (P = 0.0688);Loss of catalytic residue at R89 (P = 0.0688);.;.;

MVP

0.21

MPC

0.037

ClinPred

0.15

GERP RS

3.0

Varity_R

0.12

gMVP

0.28

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over