chr3-46408579-T-A

Position:

• chr3-46408579-T-A

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
CCRL2	NM_003965.5	c.500T>A	p.Phe167Tyr	missense_variant	2/2	ENST00000399036.4	NP_003956.2
CCRL2	NM_001130910.2	c.536T>A	p.Phe179Tyr	missense_variant	2/2		NP_001124382.1
CCRL2	XM_011534208.2	c.500T>A	p.Phe167Tyr	missense_variant	3/3		XP_011532510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCRL2	ENST00000399036.4	c.500T>A	p.Phe167Tyr	missense_variant	2/2	1	NM_003965.5	ENSP00000381994	P2

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

GnomAD3 exomes AF: 0.383 AC: 95557 AN: 249418 Hom.: 19520 AF XY: 0.389 AC XY: 52704 AN XY: 135328

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 SAS exome AF: 0.413

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

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.397

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

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.371

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
MutationTaster	Benign	1.0	P;P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3204849; hg19: chr3-46450070; COSMIC: COSV62193340; COSMIC: COSV62193340;