rs6441977

Variant names:

• chr3-46408581-G-A
• rs6441977
• NM_003965.5:c.502G>A

Variant summary

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

The NM_003965.5(CCRL2):​c.502G>A​(p.Val168Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,614,014 control chromosomes in the GnomAD database, including 16,150 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.12 (1287 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14863 hom.)
• Consequence: CCRL2 NM_003965.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 30 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=0.0016036034).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCRL2	NM_003965.5	c.502G>A	p.Val168Met	missense_variant	Exon 2 of 2	ENST00000399036.4	NP_003956.2
CCRL2	NM_001130910.2	c.538G>A	p.Val180Met	missense_variant	Exon 2 of 2		NP_001124382.1
CCRL2	XM_011534208.2	c.502G>A	p.Val168Met	missense_variant	Exon 3 of 3		XP_011532510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCRL2	ENST00000399036.4	c.502G>A	p.Val168Met	missense_variant	Exon 2 of 2	1	NM_003965.5	ENSP00000381994.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18589 AN: 152160 Hom.: 1286 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.0953

GnomAD2 exomes AF: 0.110 AC: 27379 AN: 249432 AF XY: 0.107

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0935

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.136 AC: 198770 AN: 1461736 Hom.: 14863 Cov.: 36 AF XY: 0.132 AC XY: 96264 AN XY: 727158

African (AFR) AF: 0.110 AC: 3682 AN: 33474

American (AMR) AF: 0.0932 AC: 4166 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3997 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0241 AC: 2075 AN: 86252

European-Finnish (FIN) AF: 0.151 AC: 8063 AN: 53392

Middle Eastern (MID) AF: 0.0262 AC: 151 AN: 5768

European-Non Finnish (NFE) AF: 0.152 AC: 169381 AN: 1111900

Other (OTH) AF: 0.120 AC: 7246 AN: 60396

GnomAD4 genome AF: 0.122 AC: 18608 AN: 152278 Hom.: 1287 Cov.: 33 AF XY: 0.118 AC XY: 8809 AN XY: 74468

African (AFR) AF: 0.114 AC: 4725 AN: 41550

American (AMR) AF: 0.0861 AC: 1317 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4832

European-Finnish (FIN) AF: 0.152 AC: 1613 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9937 AN: 68016

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.132 Hom.: 3127

Bravo AF: 0.118

TwinsUK AF: 0.145 AC: 536

ESP6500AA AF: 0.109 AC: 417

ESP6500EA AF: 0.148 AC: 1227

ExAC AF: 0.108 AC: 13077

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.32
DANN	Benign	0.47
DEOGEN2	Benign	0.064	T;.;T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
LIST_S2	Benign	0.0	.;T;.;T;T
MetaRNN	Benign	0.0016	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;L;.;L
PhyloP100		-1.7
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.8	N;N;N;N;N
Sift	Benign	0.086	T;T;T;T;T
Sift4G	Benign	0.11	T;T;T;T;T
Vest4		0.037
ClinPred		0.021	T
GERP RS		-11
Varity_R		0.058
gMVP		0.20
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: rs6441977; hg19: chr3-46450072; COSMIC: COSV62194015; COSMIC: COSV62194015;