chr1-159204893-T-C

Variant names:

Variant summary

Our verdict is . The variant received -10 classification points (ACMG Germline Pathogenicity v2019): 0P and 10B. BA1BP4_Moderate

The NM_002036.4(ACKR1):c.-67T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0471 (AC=75,632) in the gnomAD database across 1,605,580 control chromosomes, including 27,684 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.849. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars).

Frequency

Genomes: 𝑓 0.24 ( 14362 hom., cov: 31)

Exomes 𝑓: 0.027 ( 13322 hom. )

Consequence

ACKR1
NM_002036.4 5_prime_UTR

Scores

Clinical Significance

association; protective no assertion criteria provided P:2B:1O:1

Conservation

PhyloP100: 1.51

Publications

319 publications found

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

new If you want to explore the variant's impact on the transcript NM_002036.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -10 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.8494 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACKR1	NM_002036.4	MANE Select	c.-67T>C		5_prime_UTR	Exon 1 of 2	NP_002027.2
	ACKR1	NM_001122951.3		c.-111T>C		5_prime_UTR	Exon 1 of 2	NP_001116423.1	Q16570-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACKR1	ENST00000368122.4	TSL:1 MANE Select	c.-67T>C	5_prime_UTR	Exon 1 of 2	ENSP00000357104.1	Q16570-1
ACKR1	ENST00000368121.6	TSL:6	c.-111T>C	5_prime_UTR	Exon 1 of 2	ENSP00000357103.2	Q16570-2
ACKR1	ENST00000714112.1		c.-67T>C	5_prime_UTR	Exon 1 of 3	ENSP00000519404.1	A0AAQ5BHJ4

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36137

AN:

151932

Hom.:

14312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.822

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0903

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.00373

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.0271

AC:

39396

AN:

1453530

Hom.:

13322

Cov.:

AF XY:

0.0240

AC XY:

17337

AN XY:

723638

show subpopulations

African (AFR)

AF:

0.858

AC:

28578

AN:

33320

American (AMR)

AF:

0.0504

AC:

2253

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0227

AC:

591

AN:

26092

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39648

South Asian (SAS)

AF:

0.00608

AC:

523

AN:

86060

European-Finnish (FIN)

AF:

0.000731

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.213

AC:

1226

AN:

5760

European-Non Finnish (NFE)

AF:

0.00213

AC:

2349

AN:

1104488

Other (OTH)

AF:

0.0638

AC:

3836

AN:

60136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

652

1304

1957

2609

3261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.238

AC:

36236

AN:

152050

Hom.:

14362

Cov.:

AF XY:

0.230

AC XY:

17099

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.822

AC:

34067

AN:

41438

American (AMR)

AF:

0.0901

AC:

1377

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00914

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00374

AC:

254

AN:

68000

Other (OTH)

AF:

0.174

AC:

368

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

381

762

1143

1524

1905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.106

Hom.:

12099

Asia WGS

AF:

0.0520

AC:

183

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0000330

AC:

AN:

121668

ABraOM SABE-WGS-1171

AF:

0.178

AC:

418

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:association; protective

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DUFFY BLOOD GROUP SYSTEM, FY(a-b-) PHENOTYPE (1)

Resistance to Plasmodium vivax infection (2)

White blood cell count quantitative trait locus 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.5

PromoterAI

-0.55

Under-expression

(source)

Mutation Taster

=300/0

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over