1-159205810-G-A

Position:

chr1-159205810-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002036.4(ACKR1):c.371G>A(p.Arg124His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

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

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ACKR1
NM_002036.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.684

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026215315).

BP6

Variant 1-159205810-G-A is Benign according to our data. Variant chr1-159205810-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2274246.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACKR1	NM_002036.4 linkuse as main transcript	c.371G>A	p.Arg124His	missense_variant	2/2	ENST00000368122.4	NP_002027.2	Q16570-1Q5Y7A2
ACKR1	NM_001122951.3 linkuse as main transcript	c.377G>A	p.Arg126His	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.371G>A	p.Arg124His	missense_variant	2/2	1	NM_002036.4	ENSP00000357104.1	Q16570-1
ACKR1	ENST00000368121.6 linkuse as main transcript	c.377G>A	p.Arg126His	missense_variant	2/2	6		ENSP00000357103.2	Q16570-2
ACKR1	ENST00000435307.2 linkuse as main transcript	n.552G>A		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1 linkuse as main transcript	n.164+2000C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152268

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

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250788

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461654

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74388

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:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.046

DANN

Benign

0.54

DEOGEN2

Benign

0.056

T;T;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.75

T;.;.;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.026

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

N;N;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

1.7

N;N;N;N

REVEL

Benign

0.013

Sift

Benign

0.65

T;T;T;T

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.0020

B;B;.;.

Vest4

0.051

MutPred

0.24

Gain of glycosylation at S126 (P = 0.0955);Gain of glycosylation at S126 (P = 0.0955);.;.;

MVP

0.072

MPC

0.029

ClinPred

0.028

GERP RS

-6.5

Varity_R

0.017

gMVP

0.13

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