Variant chr3-46408581-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003965.5(CCRL2):c.502G>A(p.Val168Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,614,014 control chromosomes in the GnomAD database, including 16,150 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1287 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14863 hom. )

Consequence

CCRL2
NM_003965.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

CCRL2 (HGNC:1612): (C-C motif chemokine receptor like 2) This gene encodes a chemokine receptor like protein, which is predicted to be a seven transmembrane protein and most closely related to CCR1. Chemokines and their receptors mediated signal transduction are critical for the recruitment of effector immune cells to the site of inflammation. This gene is expressed at high levels in primary neutrophils and primary monocytes, and is further upregulated on neutrophil activation and during monocyte to macrophage differentiation. The function of this gene is unknown. This gene is mapped to the region where the chemokine receptor gene cluster is located. [provided by RefSeq, Jul 2008]

CCRL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016036034).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCRL2	NM_003965.5 link	c.502G>A	p.Val168Met	missense_variant	Exon 2 of 2	ENST00000399036.4	NP_003956.2	O00421-1B2R8C0
CCRL2	NM_001130910.2 link	c.538G>A	p.Val180Met	missense_variant	Exon 2 of 2		NP_001124382.1	O00421-2
CCRL2	XM_011534208.2 link	c.502G>A	p.Val168Met	missense_variant	Exon 3 of 3		XP_011532510.1	O00421-1B2R8C0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCRL2	ENST00000399036.4 link	c.502G>A	p.Val168Met	missense_variant	Exon 2 of 2	1	NM_003965.5	ENSP00000381994.3		O00421-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18589

AN:

152160

Hom.:

1286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.0860

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.0953

GnomAD3 exomes

AF:

0.110

AC:

27379

AN:

249432

Hom.:

1923

AF XY:

0.107

AC XY:

14445

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0935

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0224

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.136

AC:

198770

AN:

1461736

Hom.:

14863

Cov.:

AF XY:

0.132

AC XY:

96264

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0932

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0241

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.122

AC:

18608

AN:

152278

Hom.:

1287

Cov.:

AF XY:

0.118

AC XY:

8809

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.0861

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.0943

Alfa

AF:

0.136

Hom.:

2341

Bravo

AF:

0.118

TwinsUK

AF:

0.145

AC:

536

ALSPAC

AF:

0.154

AC:

593

ESP6500AA

AF:

0.109

AC:

417

ESP6500EA

AF:

0.148

AC:

1227

ExAC

AF:

0.108

AC:

13077

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.32

DANN

Benign

0.47

DEOGEN2

Benign

0.064

T;.;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.58

.;T;.;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;L;.;L

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.086

T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.095

B;B;B;.;B

Vest4

0.037

MPC

0.032

ClinPred

0.021

GERP RS

-11

Varity_R

0.058

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over