chr1-159204893-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACKR1	NM_002036.4	c.-67T>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000368122.4	NP_002027.2
ACKR1	NM_001122951.3	c.-111T>C		5_prime_UTR_variant	Exon 1 of 2		NP_001116423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACKR1	ENST00000368122	c.-67T>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_002036.4	ENSP00000357104.1
ACKR1	ENST00000368121	c.-111T>C		5_prime_UTR_variant	Exon 1 of 2			ENSP00000357103.2
CADM3-AS1	ENST00000609696.1	n.164+2917A>G		intron_variant	Intron 1 of 1	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 AC: 28578 AN: 33320

Gnomad4 AMR exome AF: 0.0504 AC: 2253 AN: 44706

Gnomad4 ASJ exome AF: 0.0227 AC: 591 AN: 26092

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39648

Gnomad4 SAS exome AF: 0.00608 AC: 523 AN: 86060

Gnomad4 FIN exome AF: 0.000731 AC: 39 AN: 53320

Gnomad4 NFE exome AF: 0.00213 AC: 2349 AN: 1104488

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.822 AC: 0.82212 AN: 0.82212

Gnomad4 AMR AF: 0.0901 AC: 0.0900706 AN: 0.0900706

Gnomad4 ASJ AF: 0.0196 AC: 0.0196192 AN: 0.0196192

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00914 AC: 0.00914001 AN: 0.00914001

Gnomad4 FIN AF: 0.000471 AC: 0.000471431 AN: 0.000471431

Gnomad4 NFE AF: 0.00374 AC: 0.00373529 AN: 0.00373529

Gnomad4 OTH AF: 0.174 AC: 0.173913 AN: 0.173913

Alfa AF: 0.106 Hom.: 12099

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

Jan 01, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Resistance to Plasmodium vivax infection Benign:1

Dec 11, 2017

OMIM

Significance: protective

Review Status: no assertion criteria provided

Collection Method: literature only

- -

White blood cell count quantitative trait locus 1 Other:1

Jan 01, 2010

OMIM

Significance: association

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.94
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

Publications

LitVar

Other links and lift over

dbSNP: rs2814778; hg19: chr1-159174683;