NM_002036.4:c.714G>A

Variant names:

• chr1-159206153-G-A
• rs36007769
• NM_002036.4:c.714G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Very_Strong BP7 BS2_Supporting

The NM_002036.4(ACKR1):​c.714G>A​(p.Gly238Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,614,250 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (36 hom.)
• Consequence: ACKR1 NM_002036.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.687
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-159206153-G-A is Benign according to our data. Variant chr1-159206153-G-A is described in ClinVar as Benign. ClinVar VariationId is 777331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.687 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 BG geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.714G>A	p.Gly238Gly	synonymous	Exon 2 of 2	NP_002027.2
	ACKR1	NM_001122951.3		c.720G>A	p.Gly240Gly	synonymous	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.714G>A	p.Gly238Gly	synonymous	Exon 2 of 2	ENSP00000357104.1	Q16570-1
	ACKR1	ENST00000368121.6	TSL:6	c.720G>A	p.Gly240Gly	synonymous	Exon 2 of 2	ENSP00000357103.2	Q16570-2
	ACKR1	ENST00000851528.1		c.714G>A	p.Gly238Gly	synonymous	Exon 3 of 3	ENSP00000521587.1

Frequencies

GnomAD3 genomes AF: 0.00485 AC: 739 AN: 152246 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00915

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00644

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00535 AC: 1345 AN: 251472 AF XY: 0.00540

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00636

Gnomad ASJ exome AF: 0.0209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00673

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.00570 AC: 8329 AN: 1461886 Hom.: 36 Cov.: 34 AF XY: 0.00577 AC XY: 4193 AN XY: 727248

African (AFR) AF: 0.00108 AC: 36 AN: 33480

American (AMR) AF: 0.00642 AC: 287 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 519 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00216 AC: 186 AN: 86258

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53414

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5768

European-Non Finnish (NFE) AF: 0.00617 AC: 6864 AN: 1112012

Other (OTH) AF: 0.00608 AC: 367 AN: 60394

GnomAD4 genome AF: 0.00486 AC: 740 AN: 152364 Hom.: 3 Cov.: 33 AF XY: 0.00466 AC XY: 347 AN XY: 74508

African (AFR) AF: 0.00151 AC: 63 AN: 41590

American (AMR) AF: 0.00914 AC: 140 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00644 AC: 438 AN: 68028

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00643 Hom.: 5

Bravo AF: 0.00575

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00851

EpiControl AF: 0.00794

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.29
DANN	Benign	0.40
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs36007769; hg19: chr1-159175943;