Genetic Variant NM_003965.5:c.5C>A (chr3-46408084-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003965.5(CCRL2):c.5C>A(p.Ala2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCRL2
NM_003965.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.15

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062209934).

BP6

Variant 3-46408084-C-A is Benign according to our data. Variant chr3-46408084-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3829241.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003965.5. 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.5C>A	p.Ala2Asp	missense	Exon 2 of 2	NP_003956.2	O00421-1
	CCRL2	NM_001130910.2		c.41C>A	p.Ala14Asp	missense	Exon 2 of 2	NP_001124382.1	O00421-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCRL2	ENST00000399036.4	TSL:1 MANE Select	c.5C>A	p.Ala2Asp	missense	Exon 2 of 2	ENSP00000381994.3	O00421-1
CCRL2	ENST00000357392.4	TSL:1	c.41C>A	p.Ala14Asp	missense	Exon 2 of 2	ENSP00000349967.4	O00421-2
CCRL2	ENST00000400880.3	TSL:1	c.5C>A	p.Ala2Asp	missense	Exon 2 of 2	ENSP00000383677.3	O00421-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000497

AC:

AN:

201236

AF XY:

0.00000921

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000649

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700840

African (AFR)

AF:

0.00

AC:

AN:

32694

American (AMR)

AF:

0.00

AC:

AN:

41040

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25404

East Asian (EAS)

AF:

0.00

AC:

AN:

38240

South Asian (SAS)

AF:

0.00

AC:

AN:

82552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089562

Other (OTH)

AF:

0.00

AC:

AN:

58886

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.20

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.016

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.36

M_CAP

Benign

0.013

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

-1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

0.56

REVEL

Benign

0.12

Sift

Benign

0.52

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.11

MutPred

0.23

Loss of catalytic residue at A2 (P = 0.0536)

MVP

0.41

MPC

0.037

ClinPred

0.021

GERP RS

-6.2

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.094

gMVP

0.28

Mutation Taster

=91/9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over