1-159206153-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002036.4(ACKR1):c.714G>A(p.Gly238=) 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, single submitter B:1
• Conservation: PhyloP100: -0.687

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 -11 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 id is 777331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.687 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACKR1	NM_002036.4	c.714G>A	p.Gly238=	synonymous_variant	2/2	ENST00000368122.4
ACKR1	NM_001122951.3	c.720G>A	p.Gly240=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACKR1	ENST00000368122.4	c.714G>A	p.Gly238=	synonymous_variant	2/2	1	NM_002036.4	P2
ACKR1	ENST00000368121.6	c.720G>A	p.Gly240=	synonymous_variant	2/2			A2
ACKR1	ENST00000435307.2	n.895G>A		non_coding_transcript_exon_variant	1/1	3
CADM3-AS1	ENST00000609696.1	n.164+1657C>T		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.00535 AC: 1345 AN: 251472 Hom.: 8 AF XY: 0.00540 AC XY: 734 AN XY: 135910

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 SAS exome AF: 0.00173

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

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00642

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00216

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.00617

Gnomad4 OTH exome AF: 0.00608

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

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.00914

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00644

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00710 Hom.: 4

Bravo AF: 0.00575

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00851

EpiControl AF: 0.00794

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.29
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs36007769; hg19: chr1-159175943;