NM_002036.4:c.67G>C

Variant names:

• chr1-159205506-G-C
• NM_002036.4:c.67G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002036.4(ACKR1):​c.67G>C​(p.Glu23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. E23K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACKR1 NM_002036.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08984655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACKR1	NM_002036.4	c.67G>C	p.Glu23Gln	missense_variant	Exon 2 of 2	ENST00000368122.4	NP_002027.2
ACKR1	NM_001122951.3	c.73G>C	p.Glu25Gln	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.67G>C	p.Glu23Gln	missense_variant	Exon 2 of 2	1	NM_002036.4	ENSP00000357104.1
ACKR1	ENST00000368121.6	c.73G>C	p.Glu25Gln	missense_variant	Exon 2 of 2	6		ENSP00000357103.2
ACKR1	ENST00000435307.2	n.248G>C		non_coding_transcript_exon_variant	Exon 1 of 1	3
CADM3-AS1	ENST00000609696.1	n.164+2304C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461730 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T;T;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.88	D;.;.;D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.090	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.71	N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.31	T;T;T;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.99	D;D;.;.
Vest4		0.094
MutPred		0.32		Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;.;
MVP		0.16
MPC		0.050
ClinPred		0.17	T
GERP RS		-0.061
Varity_R		0.16
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr1-159175296;