chr3-46408373-G-T

Variant names:

• chr3-46408373-G-T
• rs6808835
• NM_003965.5:c.294G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003965.5(CCRL2):​c.294G>T​(p.Gly98Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,613,968 control chromosomes in the GnomAD database, including 20,229 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3394 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16835 hom.)
• Consequence: CCRL2 NM_003965.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCRL2	NM_003965.5	c.294G>T	p.Gly98Gly	synonymous_variant	Exon 2 of 2	ENST00000399036.4	NP_003956.2
CCRL2	NM_001130910.2	c.330G>T	p.Gly110Gly	synonymous_variant	Exon 2 of 2		NP_001124382.1
CCRL2	XM_011534208.2	c.294G>T	p.Gly98Gly	synonymous_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.294G>T	p.Gly98Gly	synonymous_variant	Exon 2 of 2	1	NM_003965.5	ENSP00000381994.3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28254 AN: 152076 Hom.: 3388 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.140

GnomAD2 exomes AF: 0.126 AC: 31413 AN: 249448 AF XY: 0.119

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.103

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: 0.110

GnomAD4 exome AF: 0.142 AC: 208013 AN: 1461774 Hom.: 16835 Cov.: 34 AF XY: 0.138 AC XY: 100233 AN XY: 727182

Gnomad4 AFR exome AF: 0.338 AC: 11306 AN: 33476

Gnomad4 AMR exome AF: 0.105 AC: 4684 AN: 44724

Gnomad4 ASJ exome AF: 0.153 AC: 3998 AN: 26136

Gnomad4 EAS exome AF: 0.000252 AC: 10 AN: 39700

Gnomad4 SAS exome AF: 0.0244 AC: 2107 AN: 86258

Gnomad4 FIN exome AF: 0.151 AC: 8067 AN: 53420

Gnomad4 NFE exome AF: 0.152 AC: 169548 AN: 1111900

Gnomad4 Remaining exome AF: 0.134 AC: 8090 AN: 60392

GnomAD4 genome AF: 0.186 AC: 28297 AN: 152194 Hom.: 3394 Cov.: 33 AF XY: 0.180 AC XY: 13377 AN XY: 74416

Gnomad4 AFR AF: 0.338 AC: 0.337592 AN: 0.337592

Gnomad4 AMR AF: 0.105 AC: 0.105084 AN: 0.105084

Gnomad4 ASJ AF: 0.151 AC: 0.150922 AN: 0.150922

Gnomad4 EAS AF: 0.000771 AC: 0.000770713 AN: 0.000770713

Gnomad4 SAS AF: 0.0218 AC: 0.0217662 AN: 0.0217662

Gnomad4 FIN AF: 0.152 AC: 0.151813 AN: 0.151813

Gnomad4 NFE AF: 0.146 AC: 0.146421 AN: 0.146421

Gnomad4 OTH AF: 0.138 AC: 0.138258 AN: 0.138258

Alfa AF: 0.159 Hom.: 7673

Bravo AF: 0.191

Asia WGS AF: 0.0420 AC: 146 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.017
DANN	Benign	0.62
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

Publications

LitVar

Other links and lift over

dbSNP: rs6808835; hg19: chr3-46449864;