chr3-46408395-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003965.5(CCRL2):​c.316C>T​(p.Leu106Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L106I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

CCRL2
NM_003965.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11861819).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCRL2NM_003965.5 linkc.316C>T p.Leu106Phe missense_variant Exon 2 of 2 ENST00000399036.4 NP_003956.2 O00421-1B2R8C0
CCRL2NM_001130910.2 linkc.352C>T p.Leu118Phe missense_variant Exon 2 of 2 NP_001124382.1 O00421-2
CCRL2XM_011534208.2 linkc.316C>T p.Leu106Phe missense_variant Exon 3 of 3 XP_011532510.1 O00421-1B2R8C0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCRL2ENST00000399036.4 linkc.316C>T p.Leu106Phe missense_variant Exon 2 of 2 1 NM_003965.5 ENSP00000381994.3 O00421-1

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249462
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135330
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000965
AC:
141
AN:
1461866
Hom.:
0
Cov.:
34
AF XY:
0.000100
AC XY:
73
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.000124
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.0000756
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
7.3
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T;.;T;T;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.49
.;T;.;T;T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.12
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;.;L;.;L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-2.3
N;N;N;N;N
REVEL
Benign
0.068
Sift
Benign
0.076
T;T;T;T;T
Sift4G
Benign
0.30
T;T;T;T;T
Polyphen
0.64
P;P;P;.;P
Vest4
0.057
MVP
0.24
MPC
0.074
ClinPred
0.18
T
GERP RS
-3.6
Varity_R
0.089
gMVP
0.28

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.

Other links and lift over

dbSNP: rs754286699; hg19: chr3-46449886; COSMIC: COSV100644947; COSMIC: COSV100644947; API