1-159204893-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

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 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,association,protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (14362 hom., cov: 31)
  • Exomes 𝑓: 0.027 (13322 hom.)
• Consequence: ACKR1 NM_002036.4 5_prime_UTR
• Clinical Significance: Pathogenic; association; protective no assertion criteria provided P:1 B:1 O:1
• Conservation: PhyloP100: 1.51

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 -8 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, association, protective]. Clinvar id is 18395.Status of the report is no_assertion_criteria_provided, 0 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACKR1	NM_002036.4	c.-67T>C		5_prime_UTR_variant	1/2	ENST00000368122.4
ACKR1	NM_001122951.3	c.-111T>C		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACKR1	ENST00000368122.4	c.-67T>C		5_prime_UTR_variant	1/2	1	NM_002036.4	P2
ACKR1	ENST00000368121.6	c.-111T>C		5_prime_UTR_variant	1/2			A2
CADM3-AS1	ENST00000609696.1	n.164+2917A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00608

Gnomad4 FIN exome AF: 0.000731

Gnomad4 NFE exome AF: 0.00213

Gnomad4 OTH exome AF: 0.0638

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

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.0901

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00914

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00374

Gnomad4 OTH AF: 0.174

Alfa AF: 0.0519 Hom.: 3888

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Significance: Pathogenic; association; protective

Submissions summary: Pathogenic:1 Benign:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2010

- -

Resistance to Plasmodium vivax infection Benign:1

protective, no assertion criteria provided

literature only

OMIM

Dec 11, 2017

- -

White blood cell count quantitative trait locus 1 Other:1

association, no assertion criteria provided

literature only

OMIM

Jan 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	21
Dann	Benign	0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs2814778; hg19: chr1-159174683;