rs3204850

Variant names:

• chr3-46408806-A-G
• rs3204850
• NM_003965.5:c.727A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130910.2(CCRL2):​c.763A>G​(p.Ile255Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 1,614,098 control chromosomes in the GnomAD database, including 7,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.068 (526 hom., cov: 33)
  • Exomes 𝑓: 0.092 (7327 hom.)
• Consequence: CCRL2 NM_001130910.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 22 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012773871).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

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.727A>G	p.Ile243Val	missense	Exon 2 of 2	NP_003956.2
	CCRL2	NM_001130910.2		c.763A>G	p.Ile255Val	missense	Exon 2 of 2	NP_001124382.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCRL2	ENST00000399036.4	TSL:1 MANE Select	c.727A>G	p.Ile243Val	missense	Exon 2 of 2	ENSP00000381994.3
	CCRL2	ENST00000357392.4	TSL:1	c.763A>G	p.Ile255Val	missense	Exon 2 of 2	ENSP00000349967.4
	CCRL2	ENST00000400880.3	TSL:1	c.727A>G	p.Ile243Val	missense	Exon 2 of 2	ENSP00000383677.3

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10327 AN: 152142 Hom.: 526 Cov.: 33

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0598

GnomAD2 exomes AF: 0.0926 AC: 23105 AN: 249538 AF XY: 0.101

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.0403

Gnomad ASJ exome AF: 0.0608

Gnomad EAS exome AF: 0.0482

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.0867

Gnomad OTH exome AF: 0.0824

GnomAD4 exome AF: 0.0915 AC: 133802 AN: 1461838 Hom.: 7327 Cov.: 35 AF XY: 0.0960 AC XY: 69823 AN XY: 727230

African (AFR) AF: 0.0124 AC: 415 AN: 33480

American (AMR) AF: 0.0403 AC: 1804 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 1633 AN: 26136

East Asian (EAS) AF: 0.0382 AC: 1518 AN: 39700

South Asian (SAS) AF: 0.209 AC: 18026 AN: 86256

European-Finnish (FIN) AF: 0.151 AC: 8058 AN: 53420

Middle Eastern (MID) AF: 0.115 AC: 663 AN: 5768

European-Non Finnish (NFE) AF: 0.0870 AC: 96737 AN: 1111960

Other (OTH) AF: 0.0819 AC: 4948 AN: 60396

GnomAD4 genome AF: 0.0678 AC: 10320 AN: 152260 Hom.: 526 Cov.: 33 AF XY: 0.0730 AC XY: 5432 AN XY: 74420

African (AFR) AF: 0.0152 AC: 633 AN: 41558

American (AMR) AF: 0.0369 AC: 565 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5188

South Asian (SAS) AF: 0.196 AC: 946 AN: 4820

European-Finnish (FIN) AF: 0.154 AC: 1630 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5865 AN: 68034

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0773 Hom.: 1174

Bravo AF: 0.0534

TwinsUK AF: 0.0836 AC: 310

ALSPAC AF: 0.0861 AC: 332

ESP6500AA AF: 0.0170 AC: 66

ESP6500EA AF: 0.0836 AC: 690

ExAC AF: 0.0942 AC: 11391

Asia WGS AF: 0.0930 AC: 323 AN: 3478

EpiCase AF: 0.0818

EpiControl AF: 0.0816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.62
DANN	Benign	0.89
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.0040
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.016
Sift	Benign	0.32	T
Sift4G	Benign	0.33	T
Polyphen		0.046	B
Vest4		0.073
MPC		0.033
ClinPred		0.0023	T
GERP RS		0.16
Varity_R		0.065
gMVP		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3204850; hg19: chr3-46450297; COSMIC: COSV62193319; COSMIC: COSV62193319;