3-46408373-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
• Publications: 24 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003965.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCRL2	NM_003965.5	MANE Select	c.294G>T	p.Gly98Gly	synonymous	Exon 2 of 2	NP_003956.2
	CCRL2	NM_001130910.2		c.330G>T	p.Gly110Gly	synonymous	Exon 2 of 2	NP_001124382.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCRL2	ENST00000399036.4	TSL:1 MANE Select	c.294G>T	p.Gly98Gly	synonymous	Exon 2 of 2	ENSP00000381994.3
	CCRL2	ENST00000357392.4	TSL:1	c.330G>T	p.Gly110Gly	synonymous	Exon 2 of 2	ENSP00000349967.4
	CCRL2	ENST00000400880.3	TSL:1	c.294G>T	p.Gly98Gly	synonymous	Exon 2 of 2	ENSP00000383677.3

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

African (AFR) AF: 0.338 AC: 11306 AN: 33476

American (AMR) AF: 0.105 AC: 4684 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3998 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0244 AC: 2107 AN: 86258

European-Finnish (FIN) AF: 0.151 AC: 8067 AN: 53420

Middle Eastern (MID) AF: 0.0352 AC: 203 AN: 5768

European-Non Finnish (NFE) AF: 0.152 AC: 169548 AN: 1111900

Other (OTH) 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

African (AFR) AF: 0.338 AC: 14004 AN: 41482

American (AMR) AF: 0.105 AC: 1608 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4824

European-Finnish (FIN) AF: 0.152 AC: 1608 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9959 AN: 68016

Other (OTH) AF: 0.138 AC: 292 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.017
DANN	Benign	0.62
PhyloP100		-1.5
PromoterAI		-0.0059	Neutral
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: rs6808835; hg19: chr3-46449864;