dbSNP rs755978394: CCRL2:p.Thr4Pro (chr3-46407680-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130910.2(CCRL2):c.10A>C(p.Thr4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,392,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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. T4S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

CCRL2
NM_001130910.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1264709).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130910.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCRL2	NM_003965.5	MANE Select	c.-13+178A>C		intron	N/A	NP_003956.2	O00421-1
	CCRL2	NM_001130910.2		c.10A>C	p.Thr4Pro	missense	Exon 1 of 2	NP_001124382.1	O00421-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCRL2	ENST00000357392.4	TSL:1	c.10A>C	p.Thr4Pro	missense	Exon 1 of 2	ENSP00000349967.4	O00421-2
CCRL2	ENST00000399036.4	TSL:1 MANE Select	c.-13+178A>C		intron	N/A	ENSP00000381994.3	O00421-1
CCRL2	ENST00000400880.3	TSL:1	c.-13+39A>C		intron	N/A	ENSP00000383677.3	O00421-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000431

AC:

AN:

1392238

Hom.:

Cov.:

AF XY:

0.00000437

AC XY:

AN XY:

686548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30564

American (AMR)

AF:

0.00

AC:

AN:

33844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25060

East Asian (EAS)

AF:

0.00

AC:

AN:

35570

South Asian (SAS)

AF:

0.00

AC:

AN:

77414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00000557

AC:

AN:

1077140

Other (OTH)

AF:

0.00

AC:

AN:

57720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.11

(source)

DANN

Benign

0.97

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.29

M_CAP

Benign

0.023

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.86

PhyloP100

-2.3

PROVEAN

Benign

-0.15

REVEL

Benign

0.095

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.11

MutPred

0.30

Gain of catalytic residue at T4 (P = 0.0315)

MVP

0.18

MPC

0.059

ClinPred

0.18

GERP RS

-2.7

PromoterAI

0.030

Neutral

(source)

gMVP

0.40

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over