rs13962

chr1-159205737-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002036.4(ACKR1):c.298G>A(p.Ala100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,614,076 control chromosomes in the GnomAD database, including 20,888 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 Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (1346 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19542 hom.)
• Consequence: ACKR1 NM_002036.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.580

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]

CADM3-AS1 (HGNC:40812): (CADM3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016954243).
• BP6: Variant 1-159205737-G-A is Benign according to our data. Variant chr1-159205737-G-A is described in ClinVar as [Benign]. Clinvar id is 3056036.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACKR1	NM_002036.4	c.298G>A	p.Ala100Thr	missense_variant	2/2	ENST00000368122.4
ACKR1	NM_001122951.3	c.304G>A	p.Ala102Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACKR1	ENST00000368122.4	c.298G>A	p.Ala100Thr	missense_variant	2/2	1	NM_002036.4	P2
ACKR1	ENST00000368121.6	c.304G>A	p.Ala102Thr	missense_variant	2/2			A2
ACKR1	ENST00000435307.2	n.479G>A		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1	n.164+2073C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17293 AN: 152120 Hom.: 1346 Cov.: 33

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.124 AC: 30982 AN: 250858 Hom.: 2411 AF XY: 0.129 AC XY: 17429 AN XY: 135590

Gnomad AFR exome AF: 0.0241

Gnomad AMR exome AF: 0.0650

Gnomad ASJ exome AF: 0.0645

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.156 AC: 228594 AN: 1461838 Hom.: 19542 Cov.: 36 AF XY: 0.156 AC XY: 113218 AN XY: 727218

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.0683

Gnomad4 ASJ exome AF: 0.0599

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.114 AC: 17285 AN: 152238 Hom.: 1346 Cov.: 33 AF XY: 0.111 AC XY: 8296 AN XY: 74422

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.0920

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.114

Alfa AF: 0.154 Hom.: 2446

Bravo AF: 0.102

TwinsUK AF: 0.171 AC: 635

ALSPAC AF: 0.167 AC: 644

ESP6500AA AF: 0.0318 AC: 140

ESP6500EA AF: 0.171 AC: 1467

ExAC AF: 0.127 AC: 15371

Asia WGS AF: 0.0360 AC: 123 AN: 3478

EpiCase AF: 0.161

EpiControl AF: 0.163

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ACKR1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	16
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.71	T;.;.;T
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N;N;D;N
REVEL	Benign	0.13
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.97	D;D;.;.
Vest4		0.042
MPC		0.030
ClinPred		0.010	T
GERP RS		3.1
Varity_R		0.066
gMVP		0.32

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

Other links and lift over

dbSNP: rs13962; hg19: chr1-159175527; COSMIC: COSV63674404; COSMIC: COSV63674404;