NM_002036.4:c.298G>A

Variant names:

• chr1-159205737-G-A
• rs13962
• NM_002036.4:c.298G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A100S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.11 (1346 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19542 hom.)
• Consequence: ACKR1 NM_002036.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.580
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -13 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 VariationId is 3056036.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002036.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR1	NM_002036.4	MANE Select	c.298G>A	p.Ala100Thr	missense	Exon 2 of 2	NP_002027.2
	ACKR1	NM_001122951.3		c.304G>A	p.Ala102Thr	missense	Exon 2 of 2	NP_001116423.1	Q16570-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR1	ENST00000368122.4	TSL:1 MANE Select	c.298G>A	p.Ala100Thr	missense	Exon 2 of 2	ENSP00000357104.1	Q16570-1
	ACKR1	ENST00000368121.6	TSL:6	c.304G>A	p.Ala102Thr	missense	Exon 2 of 2	ENSP00000357103.2	Q16570-2
	ACKR1	ENST00000851528.1		c.298G>A	p.Ala100Thr	missense	Exon 3 of 3	ENSP00000521587.1

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

GnomAD2 exomes AF: 0.124 AC: 30982 AN: 250858 AF XY: 0.129

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 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

African (AFR) AF: 0.0228 AC: 763 AN: 33480

American (AMR) AF: 0.0683 AC: 3055 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 1566 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.121 AC: 10442 AN: 86258

European-Finnish (FIN) AF: 0.179 AC: 9560 AN: 53366

Middle Eastern (MID) AF: 0.0711 AC: 410 AN: 5768

European-Non Finnish (NFE) AF: 0.175 AC: 194664 AN: 1112010

Other (OTH) AF: 0.135 AC: 8124 AN: 60396

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

African (AFR) AF: 0.0291 AC: 1209 AN: 41538

American (AMR) AF: 0.0920 AC: 1408 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.108 AC: 521 AN: 4818

European-Finnish (FIN) AF: 0.176 AC: 1869 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11705 AN: 67996

Other (OTH) AF: 0.114 AC: 242 AN: 2116

Alfa AF: 0.151 Hom.: 3547

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ACKR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.58
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.97	D
Vest4		0.042
MPC		0.030
ClinPred		0.010	T
GERP RS		3.1
Varity_R		0.066
gMVP		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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