17-40555135-GCG-CAA

Variant names:

• chr17-40555135-GCG-CAA
• NM_001838.4:c.742_744delCGCinsTTG
• CCR7 p.Arg248Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001838.4(CCR7):​c.742_744delCGCinsTTG​(p.Arg248Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR7 NM_001838.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

Genes affected

CCR7 (HGNC:1608): (C-C motif chemokine receptor 7) The protein encoded by this gene is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. It has been shown to control the migration of memory T cells to inflamed tissues, as well as stimulate dendritic cell maturation. The chemokine (C-C motif) ligand 19 (CCL19/ECL) has been reported to be a specific ligand of this receptor. Signals mediated by this receptor regulate T cell homeostasis in lymph nodes, and may also function in the activation and polarization of T cells, and in chronic inflammation pathogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001838.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR7	NM_001838.4	MANE Select	c.742_744delCGCinsTTG	p.Arg248Leu	missense	N/A	NP_001829.1	A0N0Q0
	CCR7	NM_001301716.2		c.724_726delCGCinsTTG	p.Arg242Leu	missense	N/A	NP_001288645.1	J3KSS9
	CCR7	NM_001301717.2		c.724_726delCGCinsTTG	p.Arg242Leu	missense	N/A	NP_001288646.1	J3KSS9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR7	ENST00000246657.2	TSL:1 MANE Select	c.742_744delCGCinsTTG	p.Arg248Leu	missense	N/A	ENSP00000246657.2	P32248
	CCR7	ENST00000579344.2	TSL:1	c.724_726delCGCinsTTG	p.Arg242Leu	missense	N/A	ENSP00000462631.1	J3KSS9
	CCR7	ENST00000578085.1	TSL:3	c.553_555delCGCinsTTG	p.Arg185Leu	missense	N/A	ENSP00000463075.1	J3KTN5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-38711387;