1-159205704-C-T

Position:

chr1-159205704-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP5BP4BS1_SupportingBS2_Supporting

The NM_002036.4(ACKR1):c.265C>T(p.Arg89Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,614,216 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0099 ( 13 hom., cov: 33)

Exomes 𝑓: 0.013 ( 184 hom. )

Consequence

ACKR1
NM_002036.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP5

Variant 1-159205704-C-T is Pathogenic according to our data. Variant chr1-159205704-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 18396.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-159205704-C-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.026265323). . Strength limited to SUPPORTING due to the PP5.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00992 (1511/152340) while in subpopulation NFE AF= 0.0163 (1106/68032). AF 95% confidence interval is 0.0155. There are 13 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 13 BG geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACKR1	NM_002036.4 linkuse as main transcript	c.265C>T	p.Arg89Cys	missense_variant	2/2	ENST00000368122.4
ACKR1	NM_001122951.3 linkuse as main transcript	c.271C>T	p.Arg91Cys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACKR1	ENST00000368122.4 linkuse as main transcript	c.265C>T	p.Arg89Cys	missense_variant	2/2	1	NM_002036.4	P2	Q16570-1
ACKR1	ENST00000368121.6 linkuse as main transcript	c.271C>T	p.Arg91Cys	missense_variant	2/2			A2	Q16570-2
ACKR1	ENST00000435307.2 linkuse as main transcript	n.446C>T		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1 linkuse as main transcript	n.164+2106G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00993

AC:

1512

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00909

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.0112

AC:

2818

AN:

250772

Hom.:

AF XY:

0.0121

AC XY:

1636

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00914

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.00481

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.0128

AC:

18703

AN:

1461876

Hom.:

184

Cov.:

AF XY:

0.0130

AC XY:

9463

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00921

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.000705

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.00517

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.00992

AC:

1511

AN:

152340

Hom.:

Cov.:

AF XY:

0.00934

AC XY:

696

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00267

Gnomad4 AMR

AF:

0.00908

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00953

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.00958

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0156

AC:

134

ExAC

AF:

0.0107

AC:

1301

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0182

EpiControl

AF:

0.0197

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DUFFY BLOOD GROUP SYSTEM, FY(bwk) PHENOTYPE

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.70

T;.;.;T

MetaRNN

Benign

0.026

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;.;.

MutationTaster

Benign

0.0044

A;A;A;A

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.99

D;D;.;.

Vest4

0.062

MPC

0.14

ClinPred

0.0093

GERP RS

3.0

Varity_R

0.094

gMVP

0.32

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