ENST00000357392.4:c.13C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000357392.4(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. 13/17 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 ENST00000357392.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCRL2	NM_003965.5	c.-13+181C>A		intron_variant	Intron 1 of 1	ENST00000399036.4	NP_003956.2
CCRL2	NM_001130910.2	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 2		NP_001124382.1
CCRL2	XM_011534208.2	c.-13+181C>A		intron_variant	Intron 2 of 2		XP_011532510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCRL2	ENST00000399036.4	c.-13+181C>A		intron_variant	Intron 1 of 1	1	NM_003965.5	ENSP00000381994.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs938493750; hg19: chr3-46449174;