1-159205704-C-G

Variant names:

• chr1-159205704-C-G
• NM_002036.4:c.265C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_002036.4(ACKR1):​c.265C>G​(p.Arg89Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R89C) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACKR1 NM_002036.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-159205704-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 18396.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.15189785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACKR1	NM_002036.4	c.265C>G	p.Arg89Gly	missense_variant	Exon 2 of 2	ENST00000368122.4	NP_002027.2
ACKR1	NM_001122951.3	c.271C>G	p.Arg91Gly	missense_variant	Exon 2 of 2		NP_001116423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACKR1	ENST00000368122.4	c.265C>G	p.Arg89Gly	missense_variant	Exon 2 of 2	1	NM_002036.4	ENSP00000357104.1
ACKR1	ENST00000368121.6	c.271C>G	p.Arg91Gly	missense_variant	Exon 2 of 2	6		ENSP00000357103.2
ACKR1	ENST00000435307.2	n.446C>G		non_coding_transcript_exon_variant	Exon 1 of 1	3
CADM3-AS1	ENST00000609696.1	n.164+2106G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;T;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.76	T;.;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.13	T;T;D;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.15	B;B;.;.
Vest4		0.12
MutPred		0.33		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);.;.;
MVP		0.43
MPC		0.043
ClinPred		0.14	T
GERP RS		3.0
Varity_R		0.14
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159175494; COSMIC: COSV104677933; COSMIC: COSV104677933;