1-159204893-T-C

Variant names:

• chr1-159204893-T-C
• rs2814778
• NM_002036.4:c.-67T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PP5_Moderate BP4 BA1

The NM_001122951.3(ACKR1):​c.-111T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 1,605,580 control chromosomes in the GnomAD database, including 27,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: 𝑓 0.24 (14362 hom., cov: 31)
  • Exomes 𝑓: 0.027 (13322 hom.)
• Consequence: ACKR1 NM_001122951.3 5_prime_UTR
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 B:1 O:1
• Conservation: PhyloP100: 1.51
• Publications: 308 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 -7 ACMG points.

• PP5: Variant 1-159204893-T-C is Pathogenic according to our data. Variant chr1-159204893-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 18395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122951.3. 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.-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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36137 AN: 151932 Hom.: 14312 Cov.: 31

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.: 29 AF XY: 0.0240 AC XY: 17337 AN XY: 723638

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: 1 AN: 39648

South Asian (SAS) AF: 0.00608 AC: 523 AN: 86060

European-Finnish (FIN) AF: 0.000731 AC: 39 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

GnomAD4 genome AF: 0.238 AC: 36236 AN: 152050 Hom.: 14362 Cov.: 31 AF XY: 0.230 AC XY: 17099 AN XY: 74310

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: 68 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00914 AC: 44 AN: 4814

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10606

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.00374 AC: 254 AN: 68000

Other (OTH) AF: 0.174 AC: 368 AN: 2116

Alfa AF: 0.106 Hom.: 12099

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	DUFFY BLOOD GROUP SYSTEM, FY(a-b-) PHENOTYPE (1)
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	21
DANN	Benign	0.94
PhyloP100		1.5
PromoterAI		-0.55	Under-expression
Mutation Taster		=300/0	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs2814778; hg19: chr1-159174683;