chr3-46408579-T-A

Variant names:

• chr3-46408579-T-A
• rs3204849
• NM_003965.5:c.500T>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.500T>A​(p.Phe167Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,613,950 control chromosomes in the GnomAD database, including 121,406 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.32 (9107 hom., cov: 33)
  • Exomes 𝑓: 0.39 (112299 hom.)
• Consequence: CCRL2 NM_003965.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 35 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=5.8069887E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCRL2	NM_003965.5	c.500T>A	p.Phe167Tyr	missense_variant	Exon 2 of 2	ENST00000399036.4	NP_003956.2
CCRL2	NM_001130910.2	c.536T>A	p.Phe179Tyr	missense_variant	Exon 2 of 2		NP_001124382.1
CCRL2	XM_011534208.2	c.500T>A	p.Phe167Tyr	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.500T>A	p.Phe167Tyr	missense_variant	Exon 2 of 2	1	NM_003965.5	ENSP00000381994.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 49038 AN: 152080 Hom.: 9107 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.374

GnomAD2 exomes AF: 0.383 AC: 95557 AN: 249418 AF XY: 0.389

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.556

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.388 AC: 566593 AN: 1461752 Hom.: 112299 Cov.: 59 AF XY: 0.389 AC XY: 283176 AN XY: 727184

African (AFR) AF: 0.123 AC: 4114 AN: 33480

American (AMR) AF: 0.358 AC: 16010 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 11231 AN: 26136

East Asian (EAS) AF: 0.482 AC: 19135 AN: 39700

South Asian (SAS) AF: 0.416 AC: 35916 AN: 86256

European-Finnish (FIN) AF: 0.333 AC: 17759 AN: 53370

Middle Eastern (MID) AF: 0.524 AC: 3025 AN: 5768

European-Non Finnish (NFE) AF: 0.392 AC: 435437 AN: 1111930

Other (OTH) AF: 0.397 AC: 23966 AN: 60388

GnomAD4 genome AF: 0.322 AC: 49037 AN: 152198 Hom.: 9107 Cov.: 33 AF XY: 0.325 AC XY: 24195 AN XY: 74412

African (AFR) AF: 0.125 AC: 5208 AN: 41554

American (AMR) AF: 0.395 AC: 6044 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2836 AN: 5170

South Asian (SAS) AF: 0.425 AC: 2054 AN: 4828

European-Finnish (FIN) AF: 0.332 AC: 3521 AN: 10592

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26609 AN: 67964

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.378 Hom.: 3691

Bravo AF: 0.316

TwinsUK AF: 0.387 AC: 1434

ALSPAC AF: 0.401 AC: 1547

ESP6500AA AF: 0.127 AC: 486

ESP6500EA AF: 0.392 AC: 3245

ExAC AF: 0.380 AC: 45880

Asia WGS AF: 0.421 AC: 1463 AN: 3478

EpiCase AF: 0.423

EpiControl AF: 0.415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.069
DANN	Benign	0.69
DEOGEN2	Benign	0.075	T;.;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.50	.;T;.;T;T
MetaRNN	Benign	0.000058	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;M;.;M
PhyloP100		0.21
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.25	T;T;T;D;T
Sift4G	Benign	0.44	T;T;T;T;T
Polyphen		0.64	P;P;P;.;P
Vest4		0.046
MPC		0.090
ClinPred		0.0082	T
GERP RS		-7.8
Varity_R		0.10
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: rs3204849; hg19: chr3-46450070; COSMIC: COSV62193340; COSMIC: COSV62193340;