3-46407683-C-A

Variant names:

• chr3-46407683-C-A
• rs938493750
• ENST00000357392.4:c.13C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130910.2(CCRL2):​c.13C>A​(p.Arg5Ser) 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. 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. R5C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCRL2 NM_001130910.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048630685).

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+181C>A		intron	N/A	NP_003956.2	O00421-1
	CCRL2	NM_001130910.2		c.13C>A	p.Arg5Ser	missense	Exon 1 of 2	NP_001124382.1	O00421-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCRL2	ENST00000357392.4	TSL:1	c.13C>A	p.Arg5Ser	missense	Exon 1 of 2	ENSP00000349967.4	O00421-2
	CCRL2	ENST00000399036.4	TSL:1 MANE Select	c.-13+181C>A		intron	N/A	ENSP00000381994.3	O00421-1
	CCRL2	ENST00000400880.3	TSL:1	c.-13+42C>A		intron	N/A	ENSP00000383677.3	O00421-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0080
DANN	Benign	0.75
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.2
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.036
Sift	Benign	0.039	D
Sift4G	Benign	0.10	T
Polyphen		0.0010	B
Vest4		0.099
MutPred		0.32		Loss of MoRF binding (P = 0.0059)
MVP		0.030
MPC		0.031
ClinPred		0.075	T
GERP RS		-6.0
PromoterAI		-0.066	Neutral
gMVP		0.47
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs938493750; hg19: chr3-46449174;