3-42864624-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001296.5(ACKR2):c.122T>C(p.Val41Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,614,140 control chromosomes in the GnomAD database, including 3,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.047 ( 233 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2787 hom. )

Consequence

ACKR2
NM_001296.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

Publications

49 publications found

Variant links:

Genes affected

ACKR2 (HGNC:1565): (atypical chemokine receptor 2) This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this receptor in lymphatic endothelial cells and overexpression in vascular tumors suggested its function in chemokine-driven recirculation of leukocytes and possible chemokine effects on the development and growth of vascular tumors. This receptor appears to bind the majority of beta-chemokine family members; however, its specific function remains unknown. This gene is mapped to chromosome 3p21.3, a region that includes a cluster of chemokine receptor genes. [provided by RefSeq, Jul 2008]

ACKR2 links:

CYP8B1 (HGNC:2653): (cytochrome P450 family 8 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum membrane protein catalyzes the conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one. The balance between these two steroids determines the relative amounts of cholic acid and chenodeoxycholic acid both of which are secreted in the bile and affect the solubility of cholesterol. This gene is unique among the cytochrome P450 genes in that it is intronless. [provided by RefSeq, Jul 2008]

CYP8B1 links:

ENSG00000290317 (HGNC:):

ENSG00000290317 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027184486).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACKR2	NM_001296.5 link	c.122T>C	p.Val41Ala	missense_variant	Exon 3 of 3	ENST00000422265.6	NP_001287.2	O00590A1LP82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACKR2	ENST00000422265.6 link	c.122T>C	p.Val41Ala	missense_variant	Exon 3 of 3	1	NM_001296.5	ENSP00000416996.1		O00590
ENSG00000290317	ENST00000426937.5 link	c.-163-44169T>C		intron_variant	Intron 2 of 6	3		ENSP00000413859.1

Frequencies

GnomAD3 genomes

AF:

0.0466

AC:

7092

AN:

152154

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.0478

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0730

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0680

Gnomad OTH

AF:

0.0521

GnomAD2 exomes

AF:

0.0508

AC:

12775

AN:

251474

AF XY:

0.0522

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.0738

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0787

Gnomad NFE exome

AF:

0.0713

Gnomad OTH exome

AF:

0.0578

GnomAD4 exome

AF:

0.0577

AC:

84372

AN:

1461868

Hom.:

2787

Cov.:

AF XY:

0.0572

AC XY:

41596

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0104

AC:

347

AN:

33480

American (AMR)

AF:

0.0366

AC:

1638

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0750

AC:

1961

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0157

AC:

1354

AN:

86258

European-Finnish (FIN)

AF:

0.0781

AC:

4173

AN:

53416

Middle Eastern (MID)

AF:

0.0687

AC:

396

AN:

5768

European-Non Finnish (NFE)

AF:

0.0640

AC:

71180

AN:

1111994

Other (OTH)

AF:

0.0550

AC:

3321

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5219

10438

15658

20877

26096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2466

4932

7398

9864

12330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0465

AC:

7087

AN:

152272

Hom.:

233

Cov.:

AF XY:

0.0456

AC XY:

3396

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0108

AC:

448

AN:

41570

American (AMR)

AF:

0.0478

AC:

731

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.0128

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0730

AC:

773

AN:

10594

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0680

AC:

4623

AN:

68014

Other (OTH)

AF:

0.0516

AC:

109

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

347

693

1040

1386

1733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0606

Hom.:

1499

Bravo

AF:

0.0433

TwinsUK

AF:

0.0618

AC:

229

ALSPAC

AF:

0.0675

AC:

260

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.0677

AC:

582

ExAC

AF:

0.0507

AC:

6150

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.0649

EpiControl

AF:

0.0724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T;.;.;T;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.048

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.66

.;T;T;T;T;T

MetaRNN

Benign

0.0027

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;.;.;.;.

PhyloP100

2.0

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

D;D;.;.;.;.

REVEL

Benign

0.087

Sift

Uncertain

0.011

D;D;.;.;.;.

Sift4G

Uncertain

0.040

D;D;D;T;T;D

Polyphen

0.96

D;D;.;.;.;.

Vest4

0.068

MPC

0.57

ClinPred

0.026

GERP RS

5.5

Varity_R

0.17

gMVP

0.21

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over